Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02032823 | Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer | PHASE3 | ACTIVE NOT_RECRUITING | 1,837 | — | — | Apr 22, 2014 | May 28, 2029 | May 6, 2026 | 698 | United States, Argentina +22 |
| NCT05498155 | Study of Neoadjuvant Olaparib Monotherapy and Olaparib and Durvalumab Combination in HER2 Negative BRCAm Breast Cancer | PHASE2 | ACTIVE NOT_RECRUITING | 50 | — | — | Nov 7, 2022 | Dec 31, 2026 | Jun 10, 2025 | 37 | United States, Australia +7 |
| NCT04711824 | Study of Stereotactic Radiosurgery With Olaparib Followed by Durvalumab and Physician's Choice Systemic Therapy in Subjects With Breast Cancer Brain Metastases | PHASE1 | RECRUITING | 41 | — | — | Mar 9, 2022 | Nov 1, 2026 | Dec 23, 2025 | 7 | United States |
An IDFS event is defined as the first occurrence of loco-regional or distant recurrence or new cancer or death from any cause.
pCR is 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.
Phase I: frequency and severity of adverse events will be measured using common toxicity criteria for adverse events version 5.
Phase II: Intracranial disease control rate will be defined as the percentage of subjects with \[complete response (CR) + partial response (PR) + stable disease\] per RANO-BM criteria at 6 months after study treatment initiation.
| Arm | Type | Description |
|---|---|---|
| Olaparib | EXPERIMENTAL | Olaparib tablets 300mg b.i.d. p.o. |
| Placebo | PLACEBO_COMPARATOR | Placebo tablets b.i.d. p.o. |
| 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). |
| 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). |
| Study Treatment Arm | EXPERIMENTAL | Cycle 1 of study treatment will consist of Olaparib twice daily concurrently with stereotactic radiosurgery (SRS). Olaparib will start one week prior to SRS and continue during and following SRS (1-5 fractions) for up to 28 days total. Once the subject has recovered from SRS, Cycle 2 will be initiated with physician's choice systemic therapy and durvalumab. Cycle 2+ will equal 21 days. During Cycles 2 and 3, physician's choice systemic monotherapy will be given along with durvalumab. Each cycle will last 21 days. Imaging to evaluate intracranial and extracranial disease will be performed after Cycle 3, and subjects with response will continue with the systemic therapy and durvalumab until progression (intracranial or extracranial), unacceptable toxicity or death. |
| Name | Type | Description |
|---|---|---|
| Olaparib | DRUG | Patients will be administred olaparib orally twice daily (b.i.d.) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 ml of water |
| Placebo | DRUG | Patients will be administred matching placebo. Two (2) tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 ml of water |
| Neoadjuvant Olaparib monotherapy group | DRUG | Neoadjuvant olaparib monotherapy (300 mg BID) for four to six 28-day cycles. |
| Neoadjuvant combination therapy with olaparib plus durvalumab | COMBINATION_PRODUCT | Neoadjuvant combination therapy with olaparib (300 mg BID) plus durvalumab (1500 mg IV Q4W) for four to six 28-day cycles. |
| Stereotactic Radiosurgery | RADIATION | SRS 1-5 fractions will be given per institutional standards |
| Durvalumab | DRUG | Durvalumab 1120 mg IV over 60 minutes Day 1 of each cycle 21 day cycle. |
| Physicians Choice systemic chemotherapy | DRUG | Olaparib: 300mg PO BID; Days 1-21 Paclitaxel: 80 mg/m2 IV over 60 min; Day 1 and 8 Nab-paclitaxel:100 mg/m2 IV over 30 min; Day 1 and 8 Eribulin: 1.4 mg/m2 IV over 2-5 min; Day 1 and 8 Carboplatin: AUC 2 mg/ml/min IV over 30-60 min; Day 1 and 8 Cisplatin: 75 mg/m2 IV over 30-60 min; Day 1 Capecitabine: 1000 mg/m2 PO BID; Days 1-14 Gemcitabine: 1000 mg/m2 IV over 30 min; Day 1 and 8 Gemcitabine + Carboplatin: 1000mg/m2 IV over 30-60 min; Day 1 and 8 |
Inclusion Criteria: * Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast that is one of the following phenotypes: 1. Triple negative breast cancer defined as: ER and PgR negative AND HER2 negative (not eligible for anti-HER2 therapy) 2. ER and/or PgR positive...