Breast CancerPhase 2OlympiaNNCT05498155
Study of Neoadjuvant Olaparib Monotherapy and Olaparib and Durvalumab Combination in HER2 Negative BRCAm Breast Cancer
A Phase 2 study testing Neoadjuvant Olaparib monotherapy group and Neoadjuvant combination therapy with olaparib plus durvalumab in people with Breast Cancer, run by AstraZeneca at 36 sites in 9 countries.
Trial summary
This study to learn more about olaparib and olaparib plus durvalumab combination therapy and also to better understand the studied disease, breast cancer, and associated health problems. Olaparib is a type of drug called a PARP (poly [adenosine diphosphate-ribose] polymerase) inhibitor. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Neoadjuvant Olaparib monotherapy group and Neoadjuvant combination therapy with olaparib plus durvalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 36 sitesin 9 countries
- Study dates
- 7 Nov 2022to 16 Sep 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or Females ≥18 years
- Minimum body weight of 30 kg
- Capable of giving signed informed consent.
- Male and Female participants of childbearing potential must use effective methods of contraception
- Histologically confirmed, newly diagnosed, primary, operable, nonmetastatic invasive breast cancer with the following characteristics:
- --ER-negative or ER-low defined as IHC nuclear staining ≤10%
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- HER2-negative (not eligible for anti-HER2 therapy) defined as:
- IHC 0, 1+ without in situ hybridization OR
- In situ hybridization non-amplified with ratio less than 2.0 OR
- In situ hybridization average HER2 copy number < 6 signals/cells
- Clinical TNM staging (per AJCC 8th Edition) as follows:
- T1b (>5 mm but ≤10 mm), N0, no known metastases (M0 or MX); OR
- T1c (>10 mm but ≤20 mm), N0, no known metastases (M0 or MX); OR
- T1 (>1 mm but ≤20 mm), N1, no known metastases (M0 or MX); OR
- T2 (>20 mm but ≤50 mm), N0, no known metastases (M0 or MX).).
- Documented deleterious or suspected deleterious mutation in BRCA1 or BRCA2 from local BRCA testing using either a germline or tumour test.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Participants must have adequate organ and bone marrow function
- Participant must be willing to undergo a baseline research biopsy prior to start of study treatment.
- Participant must be willing to have any leftover tumour tissue/FFPE from the diagnostic biopsy submitted for research purposes, if available.
Who cannot join
- Any evidence of other diseases (such as severe or uncontrolled systemic diseases or active, uncontrolled infections, including but not limited to, uncontrolled ventricular arrhythmia, uncontrolled hypertension, recent [within 3 months] myocardial infarction, uncontrolled major seizure disorder, renal transplant, active bleeding diseases, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography scan
- Refractory nausea and vomiting, chronic gastrointestinal disease likely to interfere with absorption of the study medication, inability to swallow the formulated product
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease for ≥5 years before the first dose of study intervention and of low potential risk for recurrence
- Participants with MDS or AML
- For higher risk (Cohort B) participants only: Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc), autoimmune pneumonitis, and autoimmune myocarditis
- Known active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody
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- Known to have tested positive for human immunodeficiency virus unless currently on effective anti-retroviral therapy with an undetectable viral load within 6 months
- History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
- Participant must not have had any prior treatment for the current breast cancer, including surgery, chemotherapy, hormonal therapy, radiation, or experimental therapy
- For higher risk (Cohort B) participants only: Prior exposure to anti-PD1, anti-PD-L1, or anti-CTLA4 agents (ICIs); OR an agent directed to other co-inhibitory or co-stimulatory T-cell receptors
- Any concurrent anticancer treatment
- Major surgical procedure (excluding placement of vascular access, local surgery of isolated lesions, or diagnostic staging) within 2 weeks of the first dose of study intervention
- For higher risk (Cohort B) participants only: Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
- Concomitant use of:
- Known strong cytochrome P450 (CYP3A) inhibitors or moderate CYP3A inhibitors within 2 weeks prior to first dose of study intervention
- Known strong CYP3A inducers or moderate CYP3A inducers .The required washout period prior to starting study therapy is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
Trial locations and contacts
36 sites in 9 countries.
36 sites in 9 countries
Spain11 sites
Research Site
A Coruña, 15006
Research Site
Barcelona, 08036
Research Site
Barcelona, 8035
Research Site
Cáceres, 10003
Research Site
Hospitalet deLlobregat, 08907
Research Site
Lleida, 25198
Research Site
Madrid, 28041
Research Site
Málaga, 29010
Research Site
Seville, 41009
Research Site
Seville, 41013
Research Site
Valencia, 46010
Germany7 sites
Research Site
Augsburg, by, 86156
Research Site
Cologne, 50931
Research Site
Essen, 45130
Research Site
Hamburg, 20246
Research Site
Hanover, 30625
Research Site
Heidelberg, 69120
Research Site
München, 81377
United States4 sites
Research Site
Boston, Massachusetts, 02215
Research Site
Loveland, Colorado, 80537
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Portland, Oregon, 97239
Israel4 sites
Research Site
Jerusalem, 91120
Research Site
Kfar Saba, 44218
Research Site
Ramat Gan, 5262000
Research Site
Rehovot, 76100
Italy4 sites
Research Site
Bologna, 40138
Research Site
Meldola, 47014
Research Site
Modena, 41124
Research Site
Roma, 00168
About this study
Official title: A Phase II, Multicentre, Open-Label Study to Assess the Efficacy and Safety of Olaparib Monotherapy and Olaparib Plus Durvalumab Combination as Neoadjuvant Therapy in Patients With BRCA Mutations and Early Stage HER2-Negative Breast Cancer
This study to learn more about olaparib and olaparib plus durvalumab combination therapy and also to better understand the studied disease, breast cancer, and associated health problems.
Olaparib is a type of drug called a PARP (poly [adenosine diphosphate-ribose] polymerase) inhibitor. PARP inhibitors can destroy cancer cells that are not good at repairing DNA damage. Olaparib is also approved by US Food and Drug Administration (FDA), European Medicines Agency (EMA) and in other countries for treating women with BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer.
Read more
Durvalumab is a type of anticancer drug called immunotherapy that targets cancer cells by blocking the signal that prevents the immune system from seeing the cancer cell. Your immune system can then attack and kill the cancer cells. Durvalumab is approved by the FDA and the EMA for the treatment of patients with locally advanced non-small cell lung cancer after receiving chemoradiation therapy and extensive-stage small cell lung cancer in combination with chemotherapy .
Some parts of this study are experimental, which means that durvalumab and the combination of olaparib and durvalumab are still in the development stage for the treatment of breast cancer, and they are not approved for treatment of breast cancer, except for use in research studies like this.
Read the detailed description
The investigation of olaparib as monotherapy or olaparib in combination with durvalumab in patients with early stage BRCAm, oestrogen receptor (ER)-negative or ER-low, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who are candidates for neoadjuvant therapy supports the ongoing effort to identify novel agents and new drug combinations that can improve pathological complete response (pCR) rates and event-free survival (EFS). In patients at a lower risk (T1b-c/N0) of disease recurrence and a higher chance for cure, monotherapy olaparib may provide adequate neoadjuvant treatment. In contrast, monotherapy olaparib may be inadequate neoadjuvant treatment for those patients at a higher risk (T2/N0 or T1/N1) of recurrence, and the addition of an immune checkpoint inhibitor (ICI) to the neoadjuvant regimen may improve long-term outcomes as was seen in KEYNOTE-522 and GeparNuevo. However, the risk of irreversible immune-mediated adverse events (AEs) of the endocrine system due to ICI use supports the use of ICIs only in the cohort of patients at higher risk for disease recurrence. For both the lower and higher risk groups, the study treatments have the potential for the development of de-escalation strategies in this disease setting where traditional chemotherapy regimens may be avoided altogether.
While assessment of the efficacy of the combination of olaparib and durvalumab is ongoing, there are sufficient safety data available to develop a safety and tolerability profile for the combination.
- Conditions
- Breast Cancer
- Being tested
- Neoadjuvant Olaparib monotherapy group, Neoadjuvant combination therapy with olaparib plus durvalumab
- Keywords
- BRCA Mutations, Early Stage, HER2-Negative Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant Olaparib monotherapy groupDrug
Also called Cohort A
Neoadjuvant olaparib monotherapy (300 mg BID) for four to six 28-day cycles.
Neoadjuvant combination therapy with olaparib plus durvalumabCombination product
Also called Cohort B
Neoadjuvant combination therapy with olaparib (300 mg BID) plus durvalumab (1500 mg IV Q4W) for four to six 28-day cycles.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | 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). Receives: Drug: Neoadjuvant Olaparib monotherapy group |
| Cohort B | Experimental | 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). Receives: Combination Product: Neoadjuvant combination therapy with olaparib plus durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
pCR Rate of Olaparib Monotherapy and Olaparib Plus Durvalumab Combination Therapy, Assessed by Central Pathology Review
pCR = pathological complete response pCR was defined as ypT0/Tis ypN0 (ie, no invasive residual in breast and the axillary lymph nodes on evaluation of the complete resected breast specimen and all sampled regional lymph nodes) following completion of neoadjuvant systemic therapy.
Results of this outcome measure are from DCO1 (20 November 2024). The Clopper Pearson method is for the computation of the 95% confidence interval (CI).
Measured: Approx. 4 to 6 months
Secondary outcomes (7)
pCR Rate of Olaparib Monotherapy and Olaparib Plus Durvalumab Combination Therapy, Assessed by Local Pathology Review
pCR was defined as ypT0/Tis ypN0 (ie, no invasive residual in breast and the axillary lymph nodes on evaluation of the complete resected breast specimen and all sampled regional lymph nodes) following completion of neoadjuvant systemic therapy.
Results of this outcome measure are from DCO1 (20 November 2024). The Clopper Pearson method is for the computation of the 95% CI.
Measured: Approx. 4 to 6 months
RCB of Olaparib Monotherapy and Olaparib Plus Durvalumab Combination Therapy as Assessed by Central Pathology Review
RCB = residual cancer burden RCB index value using 6 variables to categorize response in 1 of 4 classes: RCB 0 (pCR), I (minimal RCB), II (moderate RCB), and III (extensive RCB). RCB III included patients who had clinical progression before surgery, and there was no central pCR performed.
Results of this outcome measure are from DCO1 (20 November 2024).
Measured: Approx. 4 to 6 months
RCB of Olaparib Monotherapy and Olaparib Plus Durvalumab Combination Therapy as Assessed by Local Pathology Review
RCB index value using 6 variables to categorize response in 1 of 4 classes: RCB 0 (pCR), I (minimal RCB), II (moderate RCB), and III (extensive RCB). RCB III included patients who had clinical progression before surgery, and there was no central pCR performed.
Results of this outcome measure are from DCO1 (20 November 2024).
Measured: Approx. 4 to 6 months
Percentage Change in Tumour Volume at Week 12 and Week 24 From Baseline
Percentage change in tumour volume at Week 12 and Week 24 from baseline was measured using magnetic resonance imaging (MRI). Baseline was defined as the most recent measurement prior to the first administration of study intervention. Percent change from baseline was defined as: (Difference in value between post-baseline volume and baseline volume) divided by baseline volume and multiplied by 100.
Results of this outcome measure are from DCO1 (20 November 2024).
Measured: Week 12 and Week 24
Number of Participants With EFS (Event-free Survival)
EFS was defined as time from the first dose of study intervention administration to any of the following events: progression of disease that precluded surgery, local or distant recurrence after surgery, second primary malignancy (breast or other invasive cancers), or death due to any cause.
Results of this outcome measure are from final DCO (16 September 2025). One of 3 subjects in AZD2281 + MEDI4736 group had a disease progression recorded in error; 2 (8.0%) participants had an EFS event of progression of disease reported in the neoadjuvant period.
Measured: Approx. 3 years
Number of Participants With AEs
AE = adverse event; ECG = electrocardiogram Data included clinical observations, ECG parameters, haematology/clinical chemistry, vital signs assessed as the number of participants with AEs.
Results of participants with AEs are from final DCO (16 September 2025).
Measured: Through study completion, approximately 34 months
Number of Participants With SAEs
SAE = serious adverse event Data included clinical observations, ECG parameters, haematology/clinical chemistry, vital signs assessed as the number of participants with AEs.
Results of participants with SAEs are from final DCO (16 September 2025).
Measured: Through study completion, approximately 34 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2022
- Study start7 Nov 2022
- Primary completion20 Nov 2024
- Study completion16 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- There will be 2 cohorts: Cohort A will consist of a lower-risk population Cohort B will consist of a higher-risk population Participants will be allocated to receive 300 mg oral olaparib twice daily as monotherapy or in combination with durvalumab 1500 mg via intravenous infusion every 4 weeks for a minimum of 4 and a maximum of six 28-day cycles before undergoing definitive surgery. Each participant will undergo definitive surgery, preferably within 6 weeks after receiving the final dose of neoadjuvant olaparib therapy, followed by standard treatment (radiation therapy, systemic therapy per institutional standards). Participants who achieve pCR at surgery, will be allowed to continue on treatment with olaparib in the adjuvant setting in lieu of standard adjuvant systemic therapy, per physician's choice. If the physician chooses adjuvant olaparib, then the total duration of olaparib therapy in the neoadjuvant and adjuvant setting should be 12 cycles.
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anitra Fielding, MBChB, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05498155
- Sponsor's protocol ID
- D931CC00001
- Other IDs
- 2023-503529-20-00, 2021-005231-22, 2023
- Acronym
- OlympiaN
- Status last verified
- Sep 2026
- First submitted
- 5 Jul 2022
- Last updated
- 25 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No