Abemaciclib + Niraparib for Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: OHSU Knight Cancer Institute

Must not be taking: PARP inhibitors, CDK 4/6 inhibitors

Disqualifiers: Metastatic disease, Inflammatory breast cancer, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 5

Duration: 8-16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining two drugs, abemaciclib (a targeted therapy) and niraparib (a PARP inhibitor), in treating a specific type of breast cancer that responds to hormones but lacks excessive HER2 protein. The trial aims to determine the optimal dose and assess how these drugs can shrink tumors before surgery by inhibiting cancer cell growth and repair. Individuals with this breast cancer profile, whose cancer has not spread beyond the breast area, and who are scheduled for chemotherapy before surgery may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you can continue taking corticosteroids if your dose is stable for at least 4 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that combining abemaciclib and niraparib has been studied before. In a previous study, taking abemaciclib at 150 mg twice a day and niraparib at 100 mg once a day proved safe enough for further testing.

Abemaciclib, already approved for treating breast cancer, supports its safety profile. It works by blocking certain proteins that help cancer cells grow. Niraparib, a PARP inhibitor, prevents cancer cells from repairing themselves, weakening them.

Like any treatment, side effects can occur. Patients in other studies have reported some, but the main goal of these early studies is to find the right balance between effectiveness and safety. While these studies don't have all the answers yet, they provide important clues about how well these drugs might work together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of abemaciclib and niraparib for breast cancer because it offers a novel approach by targeting cancer cells in two distinct ways. Abemaciclib is a CDK4/6 inhibitor that disrupts the cancer cell cycle, while niraparib is a PARP inhibitor that prevents cancer cells from repairing their DNA. This dual action could potentially be more effective than current standard treatments that typically involve hormone therapy, chemotherapy, or HER2-targeted therapy. By simultaneously tackling cell division and DNA repair, this combination may enhance treatment efficacy and provide new hope for patients with breast cancer.

What evidence suggests that abemaciclib and niraparib might be an effective treatment for breast cancer?

Research has shown that abemaciclib and niraparib might work well together to treat hormone receptor positive (HR+) and HER2 negative breast cancer. In this trial, participants will receive both drugs as part of the treatment regimen. Abemaciclib stops cancer cells from growing by blocking certain proteins they need to multiply. Niraparib, a PARP inhibitor, prevents cancer cells from repairing their DNA, making survival more difficult. Early studies found that using these two drugs together can shrink tumors before surgery. Although this combination is still under investigation, it shows promise in improving breast cancer treatment. ^{1 2 3 6 7}

Who Is on the Research Team?

Alexandra Zimmer, M.D.

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with hormone receptor positive, HER2 negative breast cancer who haven't had prior cancer treatment (except endocrine therapy) and are planning surgery. They must have satisfactory lab results, agree to use contraception if applicable, not be pregnant or breastfeeding, and can't have certain heart conditions or a history of other cancers within the last 5 years.

Inclusion Criteria

I am fully active or can carry out light work.

I had cancer before, was treated with the intent to cure, and have been cancer-free for over 5 years.

I am scheduled for chemotherapy before surgery.

Exclusion Criteria

My cancer has spread to other parts of my body.

I haven't had any cancer except for certain types in the last 5 years.

I have received treatments like surgery or chemotherapy for my cancer before joining this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib and niraparib orally. Treatment repeats every 28 days for up to 2-4 cycles.

8-16 weeks

4-8 visits (in-person)

Surgery

Participants undergo standard of care mastectomy or lumpectomy after completing treatment cycles.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery. Follow-up occurs at 30 days post-surgery, every 3 months for the first 6 months, every 6 months for 2 years, then annually for up to 5 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Niraparib Tosylate Monohydrate

Trial Overview The trial tests the combination of two drugs before surgery: Abemaciclib which blocks proteins needed for cell growth, and Niraparib which prevents tumor cells from repairing DNA damage. The goal is to see how well these work together to shrink tumors in patients with specific types of breast cancer.

How Is the Trial Designed?

Group I: Treatment (abemaciclib, niraparib) Experimental Treatment 2 Interventions

Patients receive abemaciclib PO BID and niraparib PO QD. Treatment repeats every 28 days for up to 2-4 cycles in the absence of disease progression or unacceptable toxicity. Patients who complete 4 cycles undergo standard of care mastectomy or lumpectomy. Patients demonstrating progressive disease after only 2 cycles are switched to receive standard of care chemotherapy prior to undergoing mastectomy or lumpectomy.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

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

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

In the nextMONARCH study involving women with endocrine-refractory HR+, HER2- metastatic breast cancer, abemaciclib showed a median progression-free survival (PFS) of 9.1 months when combined with tamoxifen, but this was not significantly better than the 7.4 months PFS with abemaciclib alone plus prophylactic loperamide.

The study found that the incidence and severity of diarrhea, a common side effect of abemaciclib, were manageable with dose adjustments and antidiarrheal medication, indicating that the treatment can be tolerated while maintaining its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer. Hamilton, E., Cortes, J., Ozyilkan, O., et al.[2021]

Abemaciclib combined with endocrine therapy (ET) significantly improves quality-adjusted life years (QALYs) in patients with high-risk hormone receptor positive, HER2-negative early breast cancer, with an increase of 0.99 QALYs compared to ET alone.

The treatment is considered cost-effective in Italy, with an incremental cost-effectiveness ratio of €22,651 per QALY gained, and a 99% likelihood of being cost-effective at a threshold of €30,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. Davie, A., Traoré, S., Giovannitti, M., et al.[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]

Olaparib, an oral PARP-inhibitor, significantly improves progression-free survival in HER2-negative advanced breast cancer patients with BRCA1/2 mutations compared to standard chemotherapy, based on a randomized Phase III trial.

The trial also indicated an overall survival benefit for patients who had not received prior chemotherapy for metastatic disease, highlighting olaparib's potential as an effective treatment option in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. Griguolo, G., Dieci, MV., Miglietta, F., et al.[2021]

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

Abemaciclib is an oral medication that inhibits cyclin-dependent kinases 4 and 6, specifically approved in the USA for treating advanced or metastatic breast cancer that is hormone receptor-positive and HER2-negative.

It is effective both as a combination therapy with fulvestrant for patients who have progressed after endocrine therapy and as a standalone treatment for those who have also undergone chemotherapy, highlighting its role in advanced cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. Kim, ES.[2019]

In phase III clinical trials (MONARCH 2 and MONARCH 3), abemaciclib, a CDK4 & 6 inhibitor, significantly improved progression-free survival and overall survival in women with hormone receptor positive (HR+) and HER2-negative advanced breast cancer when used in combination with endocrine therapy.

Abemaciclib demonstrated a tolerable safety profile, making it a promising treatment option for patients who have progressed after previous endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. Masuda, N., Saji, S., Kawaguchi, T., et al.[2021]

Niraparib has been approved by the FDA for patients with complete or partial response to first-line platinum-based chemotherapy, regardless of their BRCAm or HRD status, expanding treatment options for more patients.

Olaparib, in combination with bevacizumab, has also received FDA approval for patients with epithelial ovarian cancer, indicating that PARP inhibitors are now beneficial not only for BRCAm and HRD-deficient patients but also for those with HRD-proficient tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PARP inhibitors in the treatment of ovarian cancer: a review. Washington, CR., Moore, KN.[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]

In the GeparOLA trial involving 107 patients with early HER2-negative breast cancer and homologous recombination deficiency, the combination of olaparib and paclitaxel achieved a pathological complete response (pCR) rate of 55.1%, which is higher than the 48.6% pCR rate observed with paclitaxel and carboplatin.

The olaparib and paclitaxel combination was better tolerated than the carboplatin regimen, suggesting it may be a safer option for patients, particularly in younger and hormone receptor-positive subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study). Fasching, PA., Link, T., Hauke, J., et al.[2021]

Niraparib, a recently approved treatment for recurrent platinum-sensitive ovarian cancer, has demonstrated a high oral bioavailability of 72.7% in humans, indicating effective absorption when taken orally.

The study involved six patients who received a therapeutic dose of 300 mg of niraparib, followed by a small intravenous dose to measure its levels in the bloodstream, confirming its potential as a convenient oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. van Andel, L., Rosing, H., Zhang, Z., et al.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e12598

A phase 1 study of abemaciclib and niraparib as ... This phase 1 study established abemaciclib 150 mg PO BID and niraparib 100 mg PO daily as the recommended phase 2 dose for this combination.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06594679

A Study of Niraparib in Combination With Abemaciclib for ... This is an interventional trial. The goal of this clinical trial is dose finding. There are two phases: phase Ib to determine the MTD and recommended phase ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12081494/

PARP Inhibitors in the Neoadjuvant Setting This review outlines the rationale for using PARPi in the neoadjuvant setting and evaluates findings from early and ongoing clinical trials.

4. aacrjournals.org aacrjournals.org/cancerres/article/81/4_Supplement/OT-16-01/647889/Abstract-OT-16-01-A-phase-1-study-of-abemaciclib

A phase 1 study of abemaciclib and niraparib as neoadjuvant ... This is a phase I dose-finding study evaluating the combination of abemaciclib and niraparib as a neoadjuvant therapy in patients with early stage HRBC.

5. healthaffairs.org healthaffairs.org/do/10.1377/hblog20200424.131397/full/Table_1_production.pdf

Outcome of Review in Advanced or metastatic breast cancer. No added benefit. No added benefit ... Niraparib (Zejula). Maintenance treatment for recurrent epithelial ovarian ...

6. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-473384

Side Effects of New and Emerging Breast Cancer Therapies Discussion of the existing safety data is necessary, with a recent meta-analysis demonstrating a potential increased risk of recurrence with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6333551/

New Drug Updates in Solid Tumors: PARP Inhibitors ... Abemaciclib may also be used as a single agent to treat HR-positive/HER2-negative advanced/metastatic breast cancer that has progressed following endocrine ...