Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AZD4547 · 3 trials · 5 indications
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of AZD4547 monotherapy given orally to selected patients with MIBC who have progressed following prior therapy.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) given intravenously in combination with AZD4547 given orally to selected patients with MIBC who have progressed following prior therapy.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) given intravenously in combination with olaparib given orally to selected patients with MIBC who have progressed following prior therapy.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) given intravenously in combination with AZD1775 given orally to selected patients with MIBC who have progressed following prior therapy.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) monotherapy given intravenously to selected patients with MIBC who have progressed following prior therapy.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI 4736 (durvalumab) given intravenously in combination with vistusertib given orally to selected patients with MIBC who have progressed following prior therapy.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of intravenous MEDI4736 (durvalumab) in combination with intravenous AZD9150 in selected patients with MIBC who have progressed following prior therapy.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI 4736 (durvalumab) given intravenously in combination with selumetinib given orally to selected patients with MIBC who have progressed following prior therapy.
Changes from baseline in clinical chemistry parameters will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Changes from baseline in haemotology parameters will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Changes from baseline in urinalysis findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Changes from baseline in vital signs will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Changes from baseline in physical examination findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Changes from baseline in ECG findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Changes from baseline in ejection fraction determined by assessing ECHO/MUGA scans will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Changes from baseline in coagulation parameters will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Changes from baseline in lipid profile will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
| Arm | Type | Description |
|---|---|---|
| Module A: AZD4547 Monotherapy | EXPERIMENTAL | AZD4547 will be given orally twice daily until disease progression. Patients who receive AZD4547 as monotherapy will have the option to cross over to durvalumab as monotherapy at the point of objective progression, as long as the following criteria are met: * The investigator believes it is in the patient's interest to receive durvalumab; * The patient consents to the continued treatment; * It is clinically appropriate for the patient to continue on durvalumab treatment; * The patient satisfies the key eligibility criteria for receiving durvalumab treatment. |
| Module A: MEDI4736 (durvalumab) + AZD4547 | EXPERIMENTAL | AZD4547 will be given orally twice daily until disease progression. Patients will also receive MEDI 4736 (durvalumab) by IV infusion once every 4 weeks. |
| Module B: MEDI4736 (durvalumab) + Olaparib | EXPERIMENTAL | MEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. Olaparib will be given orally twice daily. |
| Module C: MEDI4736 (durvaluamb) + AZD1775 | EXPERIMENTAL | MEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. AZD1775 will be given orally in approximate 12 hour intervals over 3 days (6 doses) on Days 1-3, 8-10, and 15-17 of 28 day cycles. |
| Module D: MEDI4736 (durvalumab) monotherapy | EXPERIMENTAL | MEDI 4736 (durvalumab) will be given by IV infusion once every 4 weeks. |
| Module E: MEDI4736 (durvalumab) + Vistusertib | EXPERIMENTAL | MEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. Vistusertib will be given orally twice per day on an intermittent schedule (2 days on, 5 days off). |
| Module F: MEDI4736 (durvaluamb) + AZD9150 | EXPERIMENTAL | AZD9150 will be given as monotherapy on Days -7, -5, and -3 of a one week lead-in period. Combination dosing with IV AZD9150 followed by IV MEDI4736 (durvalumab) begins on Day 1 of each 28 day cycle. Thereafter AZD9150 is given weekly and MEDI4736 is given once every 4 weeks. |
| Module G: MEDI4736 + Selumetinib | EXPERIMENTAL | - |
| AZD4547 + exemestane | EXPERIMENTAL | Safety run-in: AZD4547 plus exemestane |
| AZD4547 + fulvestrant | EXPERIMENTAL | A Randomised phase IIa: AZD4547 plus fulvestrant |
| Placebo + fulvestrant | PLACEBO_COMPARATOR | Randomised phase IIa: Matching placebo plus fulvestrant |
| AZD4547 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| AZD4547 | DRUG | AZD4547 Monotherapy vs. MEDI4736 (durvalumab) + AZD4547 1:1 Randomization. |
| MEDI4736 | DRUG | MEDI4736 |
| Olaparib | DRUG | MEDI4736 (durvalumab) + Olaparib |
| AZD1775 | DRUG | MEDI4736 (durvalumab) + AZD1775 |
| Vistusertib | DRUG | MEDI4736 (durvalumab) + Vistusertib |
| AZD9150 | DRUG | MEDI4736 (durvalumab) + AZD9150 |
| Selumetinib | DRUG | MEDI4736 (durvalumab) + Selumetinib |
| Exemestane | DRUG | Tablet oral once daily |
| Placebo | DRUG | Tablet oral twice daily |
| Fulvestrant | DRUG | A monthly intramuscular injection of a depot formulation with a loading dose 14 days after initial administration |
Inclusion Criteria for all Modules: 1. Metastatic MIBC 2. 2nd/3rd line 3. Failed adjuvant/neo-adjuvant chemotherapy \<1 yr 4. 1 lesion ≥10 mm at baseline in the longest diameter suitable for accurate repeated measurement 5. WHO perf. status 0-1 For Module A: 1. M/F ≥25 2. Confirmation of FGFR3 mu...
AZD4547 is an investigational small molecule developed by AstraZeneca PLC (ticker AZN) for oncology indications. It has been studied in muscle invasive bladder cancer, advanced solid malignancies, and ER+ breast cancer. It remains in clinical development and is not described as an approved therapy.
AZD4547 has been studied in muscle invasive bladder cancer within a biomarker-directed Phase 1b study. That trial, NCT02546661, is an open-label, randomized, multi-drug study that enrolled 117 patients across the United States, Canada, France, Spain, and the United Kingdom, and it is currently active but not recruiting.
AZD4547 is an FGFR inhibitor, meaning it targets fibroblast growth factor receptors. Its clinical program has included FGFR inhibition alongside pharmacokinetic and biomarker assessments, including a Phase 1 study in ER+ breast cancer combining AZD4547 with fulvestrant compared with fulvestrant alone.
AstraZeneca PLC, which trades under the ticker AZN, is the developer of AZD4547. The company has sponsored the clinical studies of the compound, including trials conducted in Japan, Europe, Canada, and the United States.
AZD4547 is in Phase 1 clinical development. It is an investigational agent and is not described as FDA approved. Its studies include a Phase 1b trial in muscle invasive bladder cancer and completed Phase 1 trials in Japanese patients with advanced solid malignancies and in ER+ breast cancer.
AZD4547 has been evaluated in trials including NCT02546661, an active Phase 1b study in muscle invasive bladder cancer with 117 patients, NCT01213160, a completed Phase 1 safety and tolerability study in 40 Japanese patients, and NCT01202591, a completed Phase 1 study of AZD4547 plus fulvestrant versus fulvestrant alone in ER+ breast cancer with 127 patients.