Phase 2
Completed N=334
A Study of Neoadjuvant Letrozole + Taselisib Versus Letrozole + Placebo in Post-Menopausal Women With Breast Cancer (LORELEI)
Source: ClinicalTrials.gov NCT02273973 ↗Enrolled (actual)
334
Serious AEs
7.2%
Results posted
May 2018
Primary outcomePrimary: Percentage of Participants With Objective Response (OR) by Centrally Assessed Breast Magnetic Resonance Imaging (MRI) Via Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1 — 50.0; 39.3 percentage of participants — p=0.0490
Summary
This is a two-arm, randomized, double-blind, multicenter, pre-operative study to evaluate the effect of combining letrozole and GDC-0032 (also known as taselisib) versus letrozole and placebo in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2 (HER2) untreated, Stage I-III operable breast cancer. Participants will be randomized into one of the two treatment arms with a 1:1 randomization ratio. Letrozole at 2.5 milligrams (mg) will be dosed once daily plus either Taselisib at 4 mg (two 2-mg tablets) or placebo on a 5 days-on/ 2 days-off schedule for a total of 16 weeks.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Objective Response (OR) by Centrally Assessed Breast Magnetic Resonance Imaging (MRI) Via Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1 |
50.0; 39.3 | 0.0490 sig |
| PRIMARY Percentage of Participants With Total Pathologic Complete Response (Total pCR), Defined as Having pCR in Both Breast and Axilla, Using American Joint Committee on Cancer (AJCC) Staging System |
1.8; 0.6 | 0.3698 |
| PRIMARY Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha (PIK3CA) Mutant (MT) Participants |
56.2; 38.0 | 0.0332 sig |
| PRIMARY Percentage of Participants With Total pCR , Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA MT Participants |
1.4; 0 | 0.4803 |
| SECONDARY Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in PIK3CA Wildtype (WT) Participants |
45.7; 40.4 | 0.5017 |
| SECONDARY Percentage of Participants With Total pCR Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA WT Participants |
2.2; 1.1 | 1.0000 |
| SECONDARY Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA MT Participants |
61.6; 40.5 | 0.0115 sig |
| SECONDARY Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA WT Participants |
54.3; 51.7 | 0.7928 |
| SECONDARY Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA MT Participants |
41.1; 31.6 | 0.2659 |
| SECONDARY Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA WT Participants |
40.2; 32.6 | 0.3299 |
| SECONDARY Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA MT Participants |
74.0; 63.3 | 0.1554 |
| SECONDARY Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA WT Participants |
62.0; 59.6 | 0.7870 |
| SECONDARY Central Assessments of Changes in Ki67 Levels |
-83.81; -80.44; -75.58; -80.51 | 0.117 |
| SECONDARY Preoperative Endocrine Prognostic Index (PEPI ) Score |
— | — |
| SECONDARY Percent Change From Baseline to Surgery in Enhancing Tumor Volume as Measured by Breast MRI |
-70.60; -57.28 | 0.002 sig |
| SECONDARY Mean Score for Health-Related Quality of Life Measured by the European Organization for Research C30 (EORTC QLQ-C30) |
6.2; 5.9; 3.0; 1.9; 5.3; 3.0 | — |
| SECONDARY Mean Score for Treatment of Cancer Quality of Life Questionnaire BR23 (QLQ-BR23) |
91.8; 94.0; 2.8; 0.6; 1.2; -0.2 | — |
| SECONDARY Percentage of Participants With Adverse Events |
91.0; 83.2 | — |
Eligibility Criteria
Inclusion Criteria
- Female participants
- Postmenopausal status
- Histologically confirmed invasive breast carcinoma, with all of the following characteristics: (i) Primary tumor greater than or equal to (>/=) 2 centimeters (cm) in largest diameter (cT1-3) by MRI; (ii) Stage I to operable Stage III breast cancer; (iii) Documented absence of distant metastases (M0)
- Estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer
- Breast cancer eligible for primary surgery
- Tumor tissue from formalin-fixed paraffin-embedded cores (FFPE) core biopsy of breast primary tumor that is confirmed as evaluable for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation status by central histopathology laboratory
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Fasting glucose less than or equal to ( 470 milliseconds (msec)
- Diffusing capacity of the lungs for carbon monoxide (DLCO) <60% of the predicted values
- Clinically significant (i.e., active) cardiovascular disease, uncontrolled hypertension, unstable angina, history of myocardial infarction, cardiac failure class II-IV
- Any contraindication to MRI examination
- Active infection requiring intravenous antibiotics
- Participants requiring any daily supplemental oxygen
- Clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis
- Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or renders the participants at high risk from treatment complications
- Significant traumatic injury within 3 weeks prior to initiation of study treatment
- Major surgical procedure within 4 weeks prior to initiation of study treatment
- Inability to comply with study and follow-up procedures
- History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
Data sourced from ClinicalTrials.gov (NCT02273973). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.