Olaparib + Durvalumab for Breast Cancer

(OlympiaN Trial)

Recruiting at 59 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

50 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Olaparib and Durvalumab for breast cancer?

Research shows that the combination of Olaparib and Durvalumab, when added to standard chemotherapy, significantly increases the rate of complete cancer disappearance in patients with HER2-negative breast cancer, especially in certain high-risk groups. ^{1 2 3 4 5}

Is the combination of Olaparib and Durvalumab safe for humans?

The combination of Olaparib and Durvalumab has been studied in various trials and is generally considered safe, with some patients experiencing side effects like immune-related reactions and fatigue. In one study, no dose-limiting toxicities were recorded, and the treatment was found to be tolerable. ^{1 2 3 6 7}

How is the drug combination of Olaparib and Durvalumab unique for breast cancer treatment?

The combination of Olaparib and Durvalumab is unique because it combines a PARP inhibitor (Olaparib) with an immunotherapy drug (Durvalumab) to enhance antitumor activity, particularly in patients with BRCA-mutated breast cancer. This approach has shown improved response rates compared to standard chemotherapy, especially in certain high-risk subtypes of HER2-negative breast cancer. ^{1 2 3 7 8}

What is the purpose of this trial?

This trial is testing olaparib alone and in combination with durvalumab for early-stage breast cancer patients with specific genetic markers. Olaparib stops cancer cells from repairing DNA, while durvalumab helps the immune system attack cancer. The goal is to find better treatment options for these patients.

Research Team

Anitra Fielding, MBChB

Principal Investigator

AstraZeneca

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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]

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]

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]

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]

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]

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]

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]

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 and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. [2021]

3. United States 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. [2023]

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

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

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

I-SPY2 platform: New lessons from the olaparib and durvalumab combination in breast cancer treatment. [2021]

6. United States 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. [2022]

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

Olaparib for the treatment of breast cancer. [2019]

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

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