Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AZD9833 · 9 trials · 7 indications
PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST 1.1) or death.
PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST) or death.
The pharmacodynamic (PD) effect of AZD9833 on ER expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by immunohistochemistry (IHC) method. The percentage change was calculated from an analysis of covariance (ANCVOA) model adjusting for baseline ER score and day of on-treatment biopsy.
The PD effect of AZD9833 on ER expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by IHC method. The sensitivity analysis excluded any patients who were HER2-positive patient by central assessment as well as patients with baseline ER H-score \< 10. The percentage change was calculated from ANCVOA model adjusting for baseline ER score and day of on-treatment biopsy.
PFS was assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1. PFS was defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or received another anti-cancer therapy prior to progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.
The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic (PK) variables of: - single-dose midazolam and omeprazole, administered together * single-dose dabigatran etexilate * single-dose celecoxib
The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic variables of: * single-dose midazolam and omeprazole, administered together * single-dose dabigatran etexilate * single-dose celecoxib
The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic variables of: * single-dose midazolam and omeprazole administered together * single-dose dabigatran etexilate * single-dose celecoxib
Assessment of the total radioactivity by measuring the cumulative amount of AZD9833 excreted
Assessment of the total radioactivity, expressed as a percentage, by measuring the cumulative amount of AZD9833 excreted
Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria of AZD9833 monotherapy. \[part A only\]
Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of subjects with treatment-related adverse events assessed by CTCAE v5.0 of AZD9833 monotherapy.
To characterise the single- and multiple-dose PK of AZD9833 monotherapy.
Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of subjects with treatment-related adverse events assessed by CTCAE v4.03.
| Arm | Type | Description |
|---|---|---|
| AZD9833 + palbociclib, abemaciclib or ribociclib | EXPERIMENTAL | The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily) |
| Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib | ACTIVE_COMPARATOR | The patients will recieve anastrozole (1 mg, PO, once daily) or letrozole (2.5 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily) |
| AZD9833 + palbociclib | EXPERIMENTAL | The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (1 mg, PO, once daily) |
| Anastrozole + palbociclib | ACTIVE_COMPARATOR | The patients will recieve Anastrozole (1 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily) |
| Stage 1: AZD9833 Dose A | EXPERIMENTAL | Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 1 of the study. |
| Stage 1: AZD9833 Dose B | EXPERIMENTAL | Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 1 of the study. |
| Stage 2: AZD9833 Dose A | EXPERIMENTAL | Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 2 of the study. |
| Stage 2: AZD9833 Dose B | EXPERIMENTAL | Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 2 of the study. |
| Stage 2: AZD9833 Dose C | EXPERIMENTAL | Post-menopausal participants will receive once daily oral dose C of AZD9833 in stage 2 of the study. |
| Stage 3: AZD9833 Dose A | EXPERIMENTAL | Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 3 of the study. |
| Stage 3: AZD9833: Dose B | EXPERIMENTAL | Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 3 of the study. |
| AZD9833 Dose A | EXPERIMENTAL | The patients will receive AZD9833 (Dose A). |
| AZD9833 Dose B | EXPERIMENTAL | The patients will receive AZD9833 (Dose B). |
| AZD9833 Dose C | EXPERIMENTAL | The patients will receive AZD9833 (Dose C). |
| Fulvestrant 500 mg | ACTIVE_COMPARATOR | The patients will receive Fulvestrant (500 mg). |
| Arm A (midazolam and omeprazole) | EXPERIMENTAL | Participants will receive single oral doses of midazolam and omeprazole together (Day 1 of Treatment Periods 1 and 3) and repeated doses of AZD9833 (Days 1 to 5 of Treatment Period 2 and Day 1 of Treatment Period 3) |
| Arm B (Dabigatran etexilate) | EXPERIMENTAL | Participants will receive single oral doses of dabigatran etexilate (Day 1 of Treatment Periods 1 and 2) and single oral dose of AZD9833 (Day 1 of Treatment Period 2) |
| Arm C (Celecoxib) | EXPERIMENTAL | Participants will receive single oral doses of celecoxib (Day 1 of Treatment Periods 1 and 3) and repeated oral doses of AZD9833 (Days 1 to 5 of Treatment Period 2 and Day 1 of Treatment Period 3) |
| [14C]AZD9833 (D8532C00005) | EXPERIMENTAL | Oral Solution, 75 mg (NMT 0.67 MBq) |
| AZD9833 monotherapy dose escalation | EXPERIMENTAL | - |
| AZD9833 monotherapy dose expansion | EXPERIMENTAL | - |
| AZD9833 with palbociclib dose expansion | EXPERIMENTAL | - |
| AZD9833 with everolimus dose expansion | EXPERIMENTAL | - |
| AZD9833 monotherapy | EXPERIMENTAL | Dose escalation of AZD9833 monotherapy for patients with ER+ HER2- advanced breast cancer |
| AZD9833 with palbociclib dose escalation | EXPERIMENTAL | - |
| AZD9833 with everolimus dose escalation | EXPERIMENTAL | - |
| AZD9833 with abemaciclib (± anastrozole) dose escalation | EXPERIMENTAL | - |
| AZD9833 with abemaciclib (± anastrozole)dose expansion | EXPERIMENTAL | - |
| AZD9833 with capivasertib dose escalation | EXPERIMENTAL | - |
| AZD9833 with capivasertib dose expansion | EXPERIMENTAL | - |
| AZD9833 with ribociclib (± anastrozole) dose escalation | EXPERIMENTAL | - |
| AZD9833 with ribociclib (± anastrozole) dose expansion | EXPERIMENTAL | - |
| AZD9833 with anastrozole dose escalation | EXPERIMENTAL | - |
| AZD9833 with anastrozole dose expansion | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| AZD9833 | DRUG | Dosage formulation: AZD9833 tablets will be administered orally |
| AZD9833 Placebo | DRUG | Dosage formulation: AZD9833 placebo tablets will be administrated orally. |
| Anastrozole | DRUG | Dosage formulation: anastrozole tablets will be administered orally. |
| Anastrozole placebo | DRUG | Dosage formulation: anastrozole placebo tablets will be administrated orally. |
| Letrozole | DRUG | Dosage formulation: letrozole tablets will be administered orally. |
| Letrozole placebo | DRUG | Dosage formulation: letrozole placebo tablets will be administered orally. |
| Palbociclib | DRUG | Dosage formulation: palbociclib tablets/capsules will be administered orally |
| Abemaciclib | DRUG | Dosage formulation: abemaciclib tablets will be administered orally |
| Luteinizing hormone-releasing hormone (LHRH) agonist | DRUG | Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist. |
| Ribociclib | DRUG | Dosage formulation: ribociclib tablets will be administered orally |
| Fulvestrant | DRUG | Dosage formulation: Fulvestrant will be administered via intramuscular (IM) injection. |
| Midazolam | DRUG | Midazolam will be administered orally as a syrup once on Day 1 of Treatment Periods 1 and 3; administered together with Omeprazole |
| Omeprazole | DRUG | An Omeprazole capsule will be administered once on Day 1 of Treatment Periods 1 and 3; administered together with Midazolam |
| Dabigatran Etexilate | DRUG | A Dabigatran Etexilate capsule will be administered once on Day 1 of Treatment Periods 1 and 2 |
| Celecoxib | DRUG | A Celecoxib capsule will be administered once on Day 1 of Treatment Periods 1 and 3 |
| [14C]AZD9833 Oral Solution, 75 mg | DRUG | Oral Solution, 75 mg (NMT 0.67 MBq) - oral, fasted |
| AZD9833 with palbociclib | DRUG | Part B: AZD9833 with palbociclib dose expansion |
| AZD9833 with everolimus | DRUG | Part B: AZD9833 with everolimus dose expansion |
| AZD9833 with abemaciclib | DRUG | Part G: AZD9833 in combination with abemaciclib (± anastrozole) dose escalation |
| AZD9833 with capivasertib | DRUG | Part I: AZD9833 in combination with capivasertib dose escalation |
| AZD9833 with ribociclib | DRUG | Part K: AZD9833 in combination with ribociclib (± anastrozole) dose escalation |
| AZD9833 with anastrozole | DRUG | Part M: AZD9833 in combination with anastrozole dose escalation |
INCLUSION CRITERIA: INFORMATION FOR TRIAL PARTICIPANTS - Participants can join the trial if they: * Have advanced breast cancer that is not able to be treated with surgery or radiation; * Have an ESR1 mutation in their cancer; * Have breast cancer that is HR-positive and HER2-negative; * Are curre...
AZD9833 is an investigational small molecule being studied for the treatment of ER-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women. It is also being evaluated in healthy volunteers for drug interaction studies. The drug is in clinical development and has not been approved by regulatory authorities.
AZD9833 is being developed by AstraZeneca PLC, a biopharmaceutical company traded on the NASDAQ under the ticker symbol AZN. The company is conducting clinical trials of AZD9833 in multiple countries, including the United States, Spain, the United Kingdom, Japan, and others.
AZD9833 is in Phase 2 clinical development for advanced ER-positive HER2-negative breast cancer. It is also being studied in Phase 1 trials. The drug is investigational and has not received FDA approval. Clinical trials are active but not recruiting participants.
AZD9833 is being studied in several clinical trials. NCT03616587 is a Phase 1 study of AZD9833 alone or in combination in women with advanced breast cancer. NCT04214288 is a Phase 2 trial comparing oral AZD9833 with intramuscular fulvestrant in postmenopausal women with advanced ER-positive HER2-negative breast cancer. NCT04541433 is a completed Phase 1 study in Japanese women, and NCT05438303 is a completed drug interaction study in healthy volunteers.
AZD9833 is a small molecule designed to target the estrogen receptor in ER-positive breast cancer cells. By interacting with this receptor, it aims to inhibit estrogen-driven tumor growth. The drug is being developed as an oral therapy for patients with ER-positive, HER2-negative advanced breast cancer.
No, AZD9833 is not the same as fulvestrant. Fulvestrant is an intramuscularly administered estrogen receptor degrader used as a comparator in a Phase 2 clinical trial of AZD9833. AZD9833 is an oral investigational drug being studied as a potential alternative treatment for advanced ER-positive HER2-negative breast cancer.