Olaparib +/− Atezolizumab for Advanced Breast Cancer

Not currently recruiting at 66 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two treatments, olaparib and atezolizumab, both individually and combined, against certain types of advanced breast cancer. Olaparib targets and blocks an enzyme that aids cancer cells in repairing damaged DNA, while atezolizumab, an immunotherapy drug, helps the immune system attack cancer cells. Individuals with non-HER2-positive breast cancer that has spread or cannot be surgically removed, and who have a BRCA 1/2 mutation, might be suitable for this trial. Participants will receive one or both treatments to determine which combination most effectively stops or shrinks the cancer. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer therapy.

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).

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

Research has shown that olaparib is generally well-tolerated by people with breast cancer. One study found no evidence of harmful effects accumulating over time, making it a promising option for extended treatments.

When combined with atezolizumab, an immunotherapy drug, olaparib aims to enhance the body's immune response to cancer. Although specific safety data for this combination is still under investigation, both drugs have FDA approval for other uses, suggesting confidence in their safety.

Overall, the treatment options in this trial have demonstrated promise in other contexts, and their safety in humans is under careful monitoring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Olaparib and Atezolizumab offer a novel approach to treating advanced breast cancer. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, Olaparib is a PARP inhibitor that specifically disrupts cancer cell DNA repair mechanisms, potentially leading to cancer cell death. Atezolizumab, on the other hand, is an immunotherapy that empowers the body's immune system to recognize and destroy cancer cells. This combination aims to enhance the effectiveness of treatment by attacking the cancer on two fronts: disrupting its ability to repair itself and boosting the immune response against it.

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

Research has shown that olaparib, which participants in this trial may receive, effectively treats metastatic breast cancer. It reduced the risk of cancer growth, spread, or death by 42% compared to some chemotherapy treatments. In another study, 9% of patients treated with olaparib had a complete response, compared to 1.5% of those receiving standard therapy. In this trial, some participants will receive olaparib alone, while others will receive a combination of olaparib and atezolizumab, an immunotherapy drug. This combination may help the immune system attack cancer cells and stop their growth. The combination has shown promise in treating various types of cancer, suggesting it could also benefit breast cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Patricia M Lorusso

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

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

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 (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 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]

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, 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, 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]

Citations

1. lynparza.com lynparza.com/breast-cancer/results/metastatic-breast-cancer.html

Metastatic Breast Cancer - Clinical Study Results of ... LYNPARZA lowered the risk of cancer growing or spreading, or death by 42% compared with certain chemotherapies.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6503629/

OlympiAD final overall survival and tolerability results In the OlympiAD study, olaparib was shown to improve progression-free survival compared with chemotherapy treatment of physician's choice (TPC) in patients ...

3. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/lynparza-demonstrated-clinically-meaningful-prolonged-survival-benefit-in-early-breast-cancer-in-olympia-phase-iii-trial.html

LYNPARZA® (olaparib) demonstrated clinically meaningful ... LYNPARZA reduced the risk of invasive breast cancer recurrence, second cancers or death by 35% (HR 0.65; 95% CI; 0.53-0.78) and reduced the risk ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1706450

Olaparib for Metastatic Breast Cancer in Patients with a ... A complete response was seen in 9.0% of the patients who had measurable disease in the olaparib group and in 1.5% in the standard-therapy group.

5. astrazeneca.com astrazeneca.com/media-centre/press-releases/2024/lynparza-demonstrated-clinically-meaningful-prolonged-survival-benefit-in-early-breast-cancer-in-olympia-phase-iii-trial.html

Lynparza demonstrated clinically meaningful prolonged ... 87.5% of patients treated with Lynparza were alive at six years vs. 83.2% in the comparator arm. First and only PARP inhibitor to improve ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10948524/

Clinical effectiveness and safety of olaparib in BRCA-mutated ... The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated ...