Breast Cancer > Dostarlimab

Niraparib + Dostarlimab for Breast Cancer

Recruiting in Palo Alto (17 mi)

+8 other locations

Overseen By Erica L. Mayer, MD MPH

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Dana-Farber Cancer Institute

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

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

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.

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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.

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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.

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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

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

My cancer is estrogen or progesterone receptor positive.

My cancer's estrogen and progesterone receptor status has been tested.

I have a harmful genetic change in BRCA1, BRCA2, or PALB2.

I can swallow and keep down pills.

My breast cancer is confirmed and the tumor is at least 1.5 cm big.

My cancer is not driven by estrogen or progesterone.

My breast cancer is confirmed, not inflammatory, and the largest tumor is at least 1.5 cm.

My tumor is HER2-negative as per the tests.

I am fully active or can carry out light work.

I am having a lumpectomy and can safely receive radiation therapy.

Exclusion Criteria

I am allergic to medications similar to niraparib or dostarlimab.

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

I have had interstitial lung disease or pneumonitis.

I have a history of MDS or AML.

I have not had a blood transfusion in the last 4 weeks.

I have had a biopsy or lymph node removal before starting the study treatment.

My breast cancer is at stage IV.

I have not had major surgery in the last 3 weeks.

I do not have any severe illnesses that are not under control.

I have not taken steroids or immunosuppressants in the last 7 days.

Participant Groups

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.

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

Find A Clinic Near You

Research locations nearby Select from list below to view details:

University of Washington / Fred Hutchinson Cancer Center Seattle, WA

Johns Hopkins University Baltimore, MD

Vanderbilt-Ingram Cancer Center Nashville, TN

Yale University Cancer Center New Haven, CT

More Trial Locations

Who is running the clinical trial?

Dana-Farber Cancer Institute Lead Sponsor

GlaxoSmithKline Industry Sponsor

Translational Breast Cancer Research Consortium Collaborator

Johns Hopkins University Collaborator

References

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

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.

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

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.

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] Label="PURPOSE">To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer.

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

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.

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] 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.

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

Pharmaceutical Approval Update. [2020] Niraparib (Zejula) for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer; ocrelizumab (Ocrevus) for relapsing or primary progressive multiple sclerosis; and dupilumab (Dupixent) for moderate-to-severe atopic dermatitis.

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

Neoadjuvant study of niraparib in patients with HER2-negative, BRCA-mutated, resectable breast cancer. [2022] This single-arm pilot study (NCT03329937) evaluated neoadjuvant niraparib antitumor activity and safety in patients with localized HER2-negative, BRCA-mutated breast cancer. Twenty-one patients received niraparib 200 mg once daily in 28-day cycles. After 2 cycles, tumor response (≥30% reduction from baseline) by MRI was 90.5% and 40.0% (6 of 15) of patients who received only niraparib (2-6 cycles) had pathological complete response; no new safety signals were identified. High niraparib intratumoral concentration was observed.