Niraparib + Dostarlimab for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, Niraparib and Dostarlimab, as a pre-surgery treatment for certain types of breast cancer. It targets patients with specific genetic mutations, BRCA and PALB2, which can influence disease progression. The trial includes groups with triple-negative breast cancer (lacking three typical receptors that fuel most breast cancer growth) and estrogen receptor-positive breast cancer (where cancer cells grow in response to estrogen). Participants must have invasive breast cancer and a BRCA or PALB2 mutation. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that the combination of niraparib and dostarlimab is being tested for safety and effectiveness in breast cancer patients with specific genetic markers, such as BRCA and PALB2 mutations. Previous studies found that some patients with these mutations tolerated the combination treatment well.

Other studies with similar patient groups found the treatment generally well-tolerated, though side effects like tiredness and nausea were noted. These side effects are common with many cancer treatments. Both niraparib and dostarlimab are already used in treatments for other conditions, suggesting they are generally safe.

Prospective participants in a clinical trial for this combination should be aware that while safety findings are promising, side effects can still occur. Discussing potential risks and benefits with a healthcare provider is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Niraparib and Dostarlimab for breast cancer because they offer a novel approach to treatment. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, Niraparib is a PARP inhibitor that specifically targets cancer cells with certain genetic defects, enhancing their vulnerability to damage. Dostarlimab, on the other hand, is an immunotherapy that works by blocking a pathway used by cancer cells to evade the immune system, effectively empowering the body's natural defenses to fight the cancer. Together, these drugs could potentially offer a more targeted and less toxic treatment option for patients with triple-negative and ER+/HER2- breast cancers.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that the combination of niraparib and dostarlimab may help treat breast cancer, particularly in patients with specific genetic mutations such as BRCA and PALB2. One study found that patients with BRCA-mutated breast cancer experienced positive outcomes, including cases where no cancer was detected after treatment. Another study demonstrated that this treatment left very little cancer remaining. In this trial, participants with triple-negative breast cancer (TNBC) will be randomized to receive the combination treatment in different sequences, while an exploratory cohort of patients with ER+/HER2- breast cancer will also receive the combination. Specifically, 3 out of 18 patients with ER+/HER2- breast cancer had a complete response, meaning the cancer was no longer detectable. These findings suggest that niraparib and dostarlimab could be effective for certain types of breast cancer. ^{2 3 5 6 7}

Who Is on the Research Team?

Erica L. Mayer, MD MPH

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 (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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04584255

Niraparib + Dostarlimab In BRCA Mutated Breast Cancer This research study involves pre-operative therapy that is specifically targeted for breast cancer in individuals with BRCA and PALB2 mutations.

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/RF3-01/753144/Abstract-RF3-01-TBCRC-056-A-Phase-II-Study-of

Abstract RF3-01: TBCRC 056: A Phase II Study of ... TBCRC 056, an open-label randomized phase II study, evaluates the PARPi niraparib (N) with the anti-PD-1 antibody dostarlimab (D) in the ...

3. onclive.com onclive.com/view/neoadjuvant-niraparib-plus-dostarlimab-data-support-development-of-non-chemo-approaches-in-brca-er-breast-cancer

Neoadjuvant Niraparib Plus Dostarlimab Data Support ... New data showing pathologic complete responses (pCRs) and minimal residual disease with preoperative niraparib (Zejula) plus dostarlimab-gxly (Jemperli) ...

4. dana-farber.org dana-farber.org/clinical-trials/20-371

A phase II study of niraparib with dostarlimab therapy as ... This research study involves pre-operative therapy that is specifically targeted for breast cancer in individuals with BRCA and PALB2 mutations.

5. cancernetwork.com cancernetwork.com/view/niraparib-dostarlimab-shows-promise-in-brca-er-her2-breast-cancer

Niraparib/Dostarlimab Shows Promise in BRCA+ ER+/HER2 Of 18 patients with BRCA-mutated ER+/HER2– breast cancer, 3 had a pathological complete response when treated with niraparib plus ...

6. aacrjournals.org aacrjournals.org/cancerres/article/83/5_Supplement/OT2-09-01/717706/Abstract-OT2-09-01-TBCRC-055-A-Phase-II-Study-of

TBCRC-055: A Phase II Study of NirAparib, Dostarlimab, and ... Abstract. Background: Metastatic triple negative breast cancer (mTNBC) is associated with high recurrence and mortality rates.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04837209

Radiation, Immunotherapy and PARP Inhibitor in Triple ... This research study is looking to see whether the combination of Dostarlimab and Niraparib plus Radiation Therapy (RT) is safe and effective in participants ...