Olaparib +/− Atezolizumab for Advanced Breast Cancer

Recruiting at 59 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Brain metastases, Liver disease, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21-day cycles, repeated until disease progression or unacceptable toxicity

81 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting the study. You must stop chemotherapy 4 weeks prior, nitrosoureas or mitomycin C 6 weeks prior, and hormone therapy 2 weeks prior. Additionally, there are specific washout periods for certain drugs like strong CYP3A inhibitors (2 weeks) and inducers (3-5 weeks).

What data supports the effectiveness of the drug Olaparib in treating advanced breast cancer?

Olaparib has been shown to improve progression-free survival in patients with BRCA-mutated, HER2-negative metastatic breast cancer compared to standard chemotherapy. It is particularly effective in patients with triple-negative breast cancer, offering a clinical benefit with manageable side effects. ^{1 2 3 4 5}

What is known about the safety of Olaparib and Atezolizumab for treating advanced breast cancer?

Olaparib (Lynparza) has been used in treating breast and ovarian cancer, showing a manageable safety profile with common side effects like nausea, fatigue, and anemia. Serious side effects, such as blood disorders, occurred in a small percentage of patients. Atezolizumab (Tecentriq) safety data is not provided in the articles, but it is generally used in cancer treatments. ^{1 2 5 6 7}

How is the drug combination of Olaparib and Atezolizumab unique for treating advanced breast cancer?

The combination of Olaparib and Atezolizumab is unique because Olaparib is a PARP inhibitor that targets cancer cells with BRCA mutations, while Atezolizumab is an immunotherapy drug that helps the immune system attack cancer cells. This combination may offer a novel approach by combining targeted therapy with immunotherapy, potentially improving outcomes for patients with advanced breast cancer. ^{1 2 6 8 9}

What is the purpose of this trial?

This randomized phase II trial studies how well olaparib with or without atezolizumab work in treating patients with non-HER2-positive breast cancer that has spread to nearby tissue or lymph nodes (locally advanced), that cannot be removed by surgery (unresectable), or that has spread from where it first started (primary site) to other places in the body (metastatic). Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. It is not known whether giving olaparib with or without atezolizumab will work better in patients with non-HER2-positive breast cancer.

Research Team

Patricia M Lorusso

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

Adults with non-HER2-positive breast cancer that's locally advanced, unresectable, or metastatic and have a BRCA mutation. They must not be on certain medications, have measurable disease, good organ function, no major surgery within the last 28 days, and agree to use effective contraception.

Inclusion Criteria

My blood clotting tests are within normal limits, or I am on a stable dose of blood thinners.

Ability to understand and the willingness to sign a written informed consent document

I meet the health, organ function, and blood criteria needed to switch from single to combined therapy without full rescreening.

Exclusion Criteria

I do not have brain metastases affecting my participation.

I have autoimmune hypothyroidism and am on a stable thyroid medication dose.

I have type 1 diabetes that is under control with a stable insulin routine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib orally twice daily on days 1-21 of each cycle, with cycles repeating every 21 days. In Arm II, atezolizumab is also administered intravenously on day 1 of each cycle.

21-day cycles, repeated until disease progression or unacceptable toxicity

Regular visits for scans and sample collections

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and every 4-8 weeks for those who discontinue treatment for reasons other than disease progression.

Up to 7 years

Treatment Details

Interventions

• Atezolizumab
• Olaparib

Trial Overview The trial is testing Olaparib alone or combined with Atezolizumab in treating patients. Olaparib blocks enzymes that repair cancer cell DNA while Atezolizumab helps the immune system attack the tumor. The study aims to see which treatment works better.

Participant Groups

Group I: Arm II (olaparib, atezolizumab) Experimental Treatment 12 Interventions

Patients receive olaparib as in Arm I and atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, bone scan, and/or PET scan as well as a biopsy and blood sample collection throughout the trial. Patients may also undergo a bone marrow aspiration and biopsy on study.

Group II: Arm I (olaparib) Experimental Treatment 11 Interventions

Patients receive olaparib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to Arm II. Patients undergo an x-ray, CT scan, MRI, bone scan, and/or PET scan as well as a biopsy and blood sample collection throughout the trial. Patients may also undergo a bone marrow aspiration and biopsy on study.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

Olaparib, a PARP inhibitor, has shown significant clinical benefits in improving progression-free survival for patients with BRCA1 or BRCA2 mutated HER2 negative metastatic breast cancer compared to standard chemotherapy.

The drug has a manageable safety profile, making it a promising treatment option, particularly for triple negative breast cancer, although further research is needed to optimize its use with other therapies and identify suitable biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. Griguolo, G., Dieci, MV., Guarneri, V., et al.[2019]

In the OlympiAD study, olaparib showed a median overall survival of 19.3 months compared to 17.1 months for standard chemotherapy, although this difference was not statistically significant overall; however, it may benefit patients who had not previously received chemotherapy for metastatic breast cancer.

Olaparib was generally well-tolerated with low-grade adverse events, a low treatment discontinuation rate of 4.9%, and no increased risk of anemia with extended use, indicating its safety profile in patients with germline BRCA mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Robson, ME., Tung, N., Conte, P., 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]

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

Olaparib is an oral medication that inhibits poly (ADP-ribose) polymerase and is primarily developed for treating BRCA mutation-positive ovarian cancer, with its capsule formulation already approved in the EU and USA.

The drug is currently undergoing extensive clinical trials for various cancers, including breast, gastric, and pancreatic cancers, indicating its potential broad application in oncology beyond ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. Deeks, ED.[2020]

Olaparib, approved by the FDA for patients with advanced ovarian cancer carrying BRCA mutations, showed a 34% objective response rate in a trial of 137 patients who had undergone three or more prior chemotherapy treatments, with a median response duration of 7.9 months.

Common side effects included anemia, nausea, and fatigue, with a small risk (2%) of developing myelodysplastic syndrome or acute myeloid leukemia, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. Kim, G., Ison, G., McKee, AE., et al.[2022]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

Olaparib is an effective treatment for patients with platinum-sensitive, relapsed BRCA-mutated high-grade serous ovarian cancer, showing significant improvement in progression-free survival compared to placebo in a study of 265 patients.

The treatment is generally well tolerated, with most side effects being mild to moderate, although fatigue, anemia, and neutropenia were noted as more severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. Frampton, JE.[2016]

References

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

New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. [2019]

3. England pubmed.ncbi.nlm.nih.gov

OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. [2015]

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

Olaparib: first global approval. [2020]

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

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]

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

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. [2016]