Olaparib + Durvalumab for Breast Cancer

(OlympiaN Trial)

Not currently recruiting at 68 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, CYP3A inhibitors

Disqualifiers: Autoimmune disorders, Hepatitis, HIV, 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: 4 to 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of two treatments, olaparib and a combination of olaparib with durvalumab, against breast cancer. Olaparib targets cancer cells by preventing DNA repair, while durvalumab (Imfinzi) aids the immune system in attacking cancer cells. The trial seeks participants with newly diagnosed, operable HER2-negative breast cancer. It includes two groups: one with lower-risk tumors and another with higher-risk tumors. Participants must not have received any prior treatment for their current breast cancer. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, specifically strong or moderate CYP3A inhibitors and inducers, before starting the study. There is a washout period (time without taking certain medications) of 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.

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

Research has shown that the FDA has approved olaparib for treating certain types of breast cancer, particularly those with BRCA mutations. This approval confirms its safety for patients with these conditions. Studies have found that olaparib's side effects are generally manageable, including nausea, tiredness, and some blood-related issues.

Durvalumab, an immunotherapy drug, has received approval for certain types of lung cancer. Research indicates it aids the immune system in identifying and destroying cancer cells. In past studies, patients experienced side effects such as tiredness, cough, and skin rash, which were usually mild to moderate.

Early research suggests that using olaparib and durvalumab together is generally well-tolerated. Some side effects, like tiredness and nausea, might overlap, but no new safety issues have emerged. This suggests that the combined treatment could be considered safe based on available data, especially since each drug is already approved for other cancers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Olaparib and Durvalumab for treating breast cancer because they offer a novel approach by combining targeted therapy and immunotherapy. Olaparib is a PARP inhibitor that specifically targets cancer cells with certain genetic mutations, while Durvalumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. This combination has the potential to enhance the body’s natural defenses against cancer, offering a promising alternative to traditional chemotherapy and hormone therapy, which often focus on directly killing rapidly dividing cells. By harnessing the power of both targeted and immune-based approaches, this treatment could offer a more effective and less toxic option for patients with HER2-negative, ER-negative, or ER-low breast cancer.

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

Research has shown that using olaparib and durvalumab together yields promising results for treating certain cancers. In one study, this combination more than doubled the duration of patient response compared to chemotherapy. Another study found that 66.7% of patients with a specific type of breast cancer did not experience cancer progression for at least 24 weeks. In this trial, participants will be divided into two cohorts to evaluate the effectiveness of this combination for breast cancer. Olaparib targets cancer cells that cannot repair their own DNA, while durvalumab helps the immune system recognize and attack cancer cells. Although these treatments are approved for other cancers, researchers continue to study their combined effectiveness for breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Anitra Fielding, MBChB

Principal Investigator

AstraZeneca

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed, operable breast cancer that's not spread and has specific characteristics including a BRCA1 or BRCA2 mutation. Participants must be able to use contraception, provide consent, have good organ function, weigh at least 30 kg, and have an ECOG status of 0 or 1. Exclusions include those with certain heart conditions, active hepatitis or autoimmune diseases, HIV unless well-controlled on therapy, prior breast cancer treatments or exposure to certain drugs.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I am able to understand and sign the consent form.

I am using effective birth control methods.

Exclusion Criteria

I haven't had major surgery in the last 2 weeks.

I haven't taken immunosuppressive drugs in the last 14 days.

I am not taking any strong or moderate drugs that affect liver enzymes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib monotherapy or olaparib plus durvalumab combination therapy as neoadjuvant treatment

4 to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 months

Long-term follow-up

Participants are monitored for event-free survival and adverse events

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Olaparib

Trial Overview The study tests Olaparib alone and in combination with Durvalumab in treating HER2 negative BRCA-mutated breast cancer. Olaparib is a PARP inhibitor approved for metastatic cases; Durvalumab is an immunotherapy approved for some lung cancers. Their combined use in breast cancer treatment remains experimental.

How Is the Trial Designed?

Group I: Cohort B Experimental Treatment 1 Intervention

Cohort B will consist of a higher-risk population of participants with HER2-negative ER-negative or ER-low defined as having a tumour size of \>20 mm but ≤50 mm and N0 (T2/N0), or having a tumour size of \>1 mm but ≤20 mm and N1 (T1/N1).

Group II: Cohort A Experimental Treatment 1 Intervention

Cohort A will consist of a lower-risk population of participants with HER2-negative ER-negative or ER-low defined as having a tumour size \>5 mm and ≤20 mm and N0 (T1b-c/N0).

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

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

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 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, 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]

The I-SPY2 platform-based phase II studies have shown that combining durvalumab and olaparib with standard neoadjuvant chemotherapy significantly improves the pathological complete response rate in patients with HER2-negative breast cancer.

This treatment approach is effective regardless of the hormone receptor status, suggesting a broad applicability for these therapies in this specific breast cancer population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

I-SPY2 platform: New lessons from the olaparib and durvalumab combination in breast cancer treatment. Perez-Garcia, J., Gion, M., Cortes, J.[2021]

The combination of durvalumab (a PD-L1 inhibitor) and olaparib (a PARP inhibitor) with standard paclitaxel chemotherapy significantly increased pathologic complete response (pCR) rates in stage II/III HER2-negative breast cancer, with rates rising from 20% to 37% overall.

While DOP showed enhanced efficacy, particularly in high-risk hormone receptor-positive/HER2-negative patients (pCR 64% vs. 22%), it also resulted in a higher incidence of immune-related grade 3 adverse events (12.3% vs. 1.3% in the control group).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial. Pusztai, L., Yau, C., Wolf, DM., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In a phase I study involving 26 women with recurrent cancers, the combination of the PD-L1 inhibitor durvalumab with olaparib or cediranib was found to be tolerable and showed promising anti-tumor activity, with an 83% disease control rate for the durvalumab plus olaparib group.

The recommended phase II doses were established as durvalumab 1,500 mg every 4 weeks with olaparib 300 mg twice daily, or cediranib 20 mg on an intermittent schedule, indicating that these combinations could be viable options for further investigation in treating recurrent women's cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of the Programmed Death-Ligand 1 Inhibitor Durvalumab in Combination With Poly (ADP-Ribose) Polymerase Inhibitor Olaparib or Vascular Endothelial Growth Factor Receptor 1-3 Inhibitor Cediranib in Women's Cancers: A Dose-Escalation, Phase I Study. Lee, JM., Cimino-Mathews, A., Peer, CJ., et al.[2022]

In a study involving 34 patients with BRCA1 or BRCA2 mutated metastatic breast cancer, the combination of olaparib and durvalumab demonstrated promising antitumor activity, with 80% of patients showing disease control at 12 weeks.

The treatment was generally safe, with 32% of patients experiencing grade 3 or worse adverse events, but no treatment-related deaths were reported, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Domchek, SM., Postel-Vinay, S., Im, SA., et al.[2021]

Citations

1. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/lynparza-olaparib-and-imfinzi-durvalumab-demonstrated-strong-clinical-benefit-and-more-than-doubled-median-duration-of-response-vs-chemotherapy-in-patients-with-mismatch-repair-proficient-advanced-or-recurrent-endometrial-cancer.html

LYNPARZA® (olaparib) and IMFINZI® (durvalumab) ... LYNPARZA (olaparib) and IMFINZI (durvalumab) demonstrated strong clinical benefit and more than doubled median duration of response vs. chemotherapy.

2. onclive.com onclive.com/view/olaparib-durvalumab-fulvestrant-combo-meets-pfs-end-point-in-hrr-altered-or-msi-er-her2-breast-cancer

Olaparib/Durvalumab/Fulvestrant Combo Meets PFS End ... Olaparib, durvalumab, and fulvestrant produced a 66.7% 24-week PFS rate in patients with endocrine-resistant, ER-positive, HER2-negative breast cancer.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419594030

Phase II study of olaparib (O) and durvalumab (D) ... In OlympiAD (single-agent olaparib), median duration of response (DoR) and median progression-free survival (PFS) were 6.4 months (m) and 7.0 m, respectively.

4. targetedonc.com targetedonc.com/view/durvalumab-plus-olaparib-improve-responses-with-neoadjuvant-chemo-in-high-risk-her2-negative

Durvalumab Plus Olaparib Improve Responses with ... Data showed that in all patients with HER2-negative breast cancer, the predicted probability of pCR with the combination and with paclitaxel ...

5. aacrjournals.org aacrjournals.org/cancerres/article/79/4_Supplement/PD5-04/640266/Abstract-PD5-04-An-open-label-phase-II-basket

Abstract PD5-04: An open-label, phase II basket study of ... Here, the objective was to assess the efficacy and safety of olaparib in combination with durvalumab (Imfinzi), a PD-L1 agent, in gBRCAm HER2- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02484404

NCT02484404 | Phase I/II Study of the Anti-Programmed ... - Durvalumab is a drug that may help people s immune systems respond to and kill cancer cells. Olaparib is a drug that may inhibit repairing DNA damage of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8655309/

Emerging Role of PARP Inhibitors in Metastatic Triple ... In first-line subgroup, 40.8% of patients in the olaparib arm were alive at 3 years compared with 12.8% of patients in the TPC arm. No new safety data and no ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02734004

NCT02734004 | A Phase I/II Study of MEDI4736 in ... The purpose of this study is to look at the effectiveness, safety, and antitumor activity of study drugs MEDI4736 in combination with olaparib (modules 1, ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1556086419303612

Durvalumab in Combination with Olaparib in Patients ... Here we report the efficacy, safety, and biomarker results from patients with SCLC treated with durvalumab plus olaparib. Patients and Methods. Eligible ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11064785/

Durvalumab with olaparib and paclitaxel for high-risk HER2 ... Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial