Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as ISIS 481464, Danvatirsen
AZD9150 · 4 trials · 5 indications
The Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) will be determined by assessment of the incidence of dose-limiting toxicities (DLTs). DLTs may come from the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), the change from baseline in vital signs, clinical chemistry, haemotology, and urinalysis parameters will be evaluated for each treatment arm in Part A of the study.
Pharmacokinetic parameters will be derived from the measured plasma concentration of AZD9150. The area under the plasma concentration versus time curve \[AUC(ss)\] will be compared in subjects receiving AZD9150 subcutaneoulsy vs. intravenously.
Pharmacokinetic parameters will be derived from the measured plasma concentration of AZD9150. The minimum plasma concentration of AZD9150 at steady state \[Ctrough(ss)\] will be determined for subjects receiving AZD9150 once per week in combination with durvalumab.
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
After completion of DLT period (35 days) for the maximum dose cohort. A CRM-based approach was used to identify the set of dose combinations where the incidence of DLT was ≤ 33%. The dose with expected DLT incidence closest and below 0.33 at this point was the "model estimated" MTD. During trial execution, the Safety Review Committee (SRC) determined the MTD.
After completion of DLT period (35 days) for the maximum dose cohort. A CRM-based approach was used to identify the set of dose combinations where the incidence of DLT was ≤ 33%. The dose with expected DLT incidence closest and below 0.33 at this point was the "model estimated" MTD. During trial execution, the Safety Review Committee (SRC) determined the MTD.
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
proportion of patients who have an objective response at a given visit. ORR will be summarised by treatment group. Objective rate is defined as a CR or PR according to RECIST 1.1.
Cycle 1 was defined as 3 loading doses given on Days 1, 3, and 5 followed by 3 weekly doses given on Days 8, 15, and 22.
| Arm | Type | Description |
|---|---|---|
| Arm A1 | EXPERIMENTAL | Patients will receive AZD9150 every two weeks (Q2W) + durvalumab every four weeks (Q4W). There will be a 1 week AZD9150 lead-in prior to durvalumab dosing. |
| Arm A2 | EXPERIMENTAL | Patients will receive AZD9150 once weekly (QW) + durvalumab every three weeks (Q3W) + Cisplatin on Day 1 + 5-flourouracil (5-FU) on Days 1 to 4. This regimen will be repeated every 3 weeks for up to 18 weeks. There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing. |
| Arm A3 | EXPERIMENTAL | Depending on the results of Arm A2, Arm A3 may not be conducted. If Arm A3 is conducted, patients will receive AZD9150 every two weeks (Q2W) + durvalumab every three weeks (Q3W) + cisplatin on Day 1 + 5-flourouracil (5-FU) over Days 1 to 4. This regimen will be repeated every 3 weeks for up to 18 weeks. There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing. |
| Arm A4 | EXPERIMENTAL | Patients will receive AZD9150 every two weeks (Q2W) + durvalumab every three weeks (Q3W) + gemcitabine on Days 1 and 8. This regimen will be repeated every 3 weeks. In addition, the following will be added to the regimen: * For cisplatin-eligible patients: cisplatin on Day 1 (every 3 weeks for up to 12-18 weeks); or * For cisplatin ineligible patients: carboplatin on Day 1 and Day 8 (every 3 weeks for up to 12-18 weeks) There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing. |
| Arm A5 | EXPERIMENTAL | Patients will receive AZD9150 every two weeks (Q2W) plus durvalumab every three weeks (Q3W) plus carboplatin on Day 1 plus nab-paclitaxel on Days 1, 8, and 15 (every 3 weeks for up to 12-18 weeks). There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing. |
| Arm D: AZD9150 SC | EXPERIMENTAL | Part D will compare the single and steady state pharmacokinetics of AZD9150 given subcutaneously (SC) QW to AZD9150 given by IV QW in combination with durvalumab 1500 mg Q4W. Patients will be randomly assigned to either SC or IV AZD9150. |
| Arm D: AZD9150 IV | EXPERIMENTAL | Part D will compare the single and steady state pharmacokinetics of AZD9150 given subcutaneously (SC) QW to AZD9150 given by IV QW in combination with durvalumab 1500 mg Q4W. Patients will be randomly assigned to either SC or IV AZD9150. |
| C1:AZD9150, C2:AZD9150+Durvalumab | EXPERIMENTAL | After confirmed safety with Cohort 1, Cohort 2 will open |
| Part A1: AZD9150 / MEDI4736 | EXPERIMENTAL | Patients allocated in cohort of arm A1 (AZD9150/MEDI4736 will be evaluated for DLT until an MTD is achieved. |
| Part A2: AZD5069 / MEDI4736 | EXPERIMENTAL | Patients allocated in cohort of arm A2 (AZD5069/MEDI4736 will be evaluated for DLT until an MTD is achieved. |
| Part B1:AZD9150+MEDI4736:PDL1 pretreated | EXPERIMENTAL | Patients in arm B1 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. |
| Part B2:AZD5069+MEDI4736:PDL1 pretreated | EXPERIMENTAL | Patients in arm B2 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. |
| Part B3: AZD9150+MED4736:naiive 2L | EXPERIMENTAL | Patients in arm B3 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. |
| Part B4:AZD5069+MEDI4736:naiive patients | EXPERIMENTAL | Patients in arm B4 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. |
| Part B5: AZD9150 in naiive patients | EXPERIMENTAL | Patients in arm B5 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival |
| Part B6:AZD5069 in naiive patients | EXPERIMENTAL | Patients in arm B6 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival |
| Part A3: AZD5069/MEDI4736 | EXPERIMENTAL | Patients allocated in cohort of arm A3 (AZD5069/MEDI4736) will be evaluated for DLT and viability as alternate dosing option for Phase 2 studies |
| Part A4: AZD9150/Treme/MEDI4736 | EXPERIMENTAL | Patients allocated in cohort of arm A4 (AZD9150/treme/MEDI4736) will be evaluated for DLT and MTD |
| Part A5: AZD5069/Treme/MEDI4736 | EXPERIMENTAL | Patients allocated in cohort of arm A5 (AZD5069/treme/MEDI4736) will be evaluated for DLT and MTD. |
| Part A6: AZD9150/MEDI4736 | EXPERIMENTAL | Patients allocated in cohort of arm A6 (AZD9150/MEDI4736) will be evaluated for safety, PK and PD. |
| Part A7: AZD5069/MEDI4736 | EXPERIMENTAL | Patients allocated in cohort of arm A7 (AZD5069/MEDI4736) will be evaluated for safety, PK and PD. |
| Part B7: AZD9150+MEDI4736: naiive 1L | EXPERIMENTAL | Patients in Arm B7 will be evaluated for efficacy until disease progression and then followed up for safety and survival |
| Part B8: AZD9150 (every other week)+MEDI4736: naive 1L | EXPERIMENTAL | Patients in Arm B8 will be evaluated for efficacy until disease progression and then followed up for safety and survival |
| AZD9150 | EXPERIMENTAL | There are two parts, dose escalation phase (Part A) and dose expansion phase (Part B). |
| Name | Type | Description |
|---|---|---|
| AZD9150 | DRUG | AZD9150 will be administered as a 1-hour intravenous infusion either weekly (QW) or every two weeks (Q2W), depending on which arm the patient is enrolled in. AZD9150 will be provided as a liquid drug product in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement. |
| Durvalumab | DRUG | Durvalumab will be administered as a 1-hour intravenous infusion either every three weeks (Q3W) or every four weeks (Q4W), depending on which arm the patient is enrolled in. Durvalumab will be provided as a solution in clear glass vials. Each vial will be labelled in accordance with GMP Annex 13 and per country regulatory requirement. |
| Cisplatin | DRUG | Cisplatin will be infused over 30-60 minutes on Day 1. |
| 5-Flourouracil | DRUG | 5-flourouracil will be continuously infused over Days 1 to 4 every three weeks for up to 18 weeks. |
| Carboplatin | DRUG | Carboplatin will be infused over 30 to 60 minutes on Days 1, 8, and 15, depending on which arm the patient is enrolled in, for up to 18 weeks. |
| Gemcitabine | DRUG | Gemcitabine will be infused over 30 minutes on Days 1 and 8 for up to 18 weeks. |
| Nab-paclitaxel | DRUG | Nab-paclitaxel will be infused over 30 to 40 minutes on Days 1, 8, and 15 for up to 18 weeks. |
| AZD9150, Durvalumab | DRUG | After confirmed safety with Cohort 1, Cohort 2 will open. Patients allocated in each cohort will be evaluated for DLT |
| MEDI4736 | DRUG | MEDI4736 |
| AZD5069 | DRUG | AZD5069 |
| tremelimumab (treme) | DRUG | tremelimumab |
Inclusion Criteria Subjects are eligible to be included in the study only if all of the following inclusion criteria and none of the exclusion criteria apply. 1. Signed and dated informed consent. For inclusion in the optional pharmacogenetic research, patients must provide informed consent for th...
AZD9150 is an investigational small molecule developed by AstraZeneca PLC (ticker AZN) for oncology. It has been studied in Phase 1 clinical trials in advanced solid tumors, advanced solid malignancies, metastatic squamous cell carcinoma of the head and neck, and advanced adult hepatocellular carcinoma. It is not an approved therapy and remains in clinical development.
AZD9150 has been studied in Phase 1 trials for advanced adult hepatocellular carcinoma, advanced solid malignancies, advanced solid tumors, and metastatic squamous cell carcinoma of the head and neck. These studies are complete, and the drug is investigational rather than an approved treatment for any indication.
AZD9150 is developed by AstraZeneca PLC, which trades under the ticker AZN. The company sponsored the Phase 1 studies of the drug in advanced solid tumors, advanced solid malignancies, head and neck cancer, and hepatocellular carcinoma.
AZD9150 is in Phase 1 development. All of its recorded trials are Phase 1 studies and all have completed, with no active trials ongoing. It is an investigational agent and is not approved by the FDA for any indication.
AZD9150 has been evaluated in completed Phase 1 trials including NCT03421353 in advanced solid tumors and non-small-cell lung cancer, NCT03394144 in Japanese patients with advanced solid malignancies, NCT02499328 in advanced solid tumors and head and neck cancer, and NCT01839604 in advanced hepatocellular carcinoma.
No. AZD9150 and durvalumab are separate agents. Several Phase 1 studies combined AZD9150 with durvalumab, also known as MEDI4736, in advanced solid tumors, head and neck cancer, and non-small-cell lung cancer, but they are distinct drugs studied together in combination regimens.