Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Lynparza
Olaparib Pill · 1 trial · 1 indication
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 for all cohorts.
Objective response rate (CR+PR) of the combination of AZD6738 and olaparib in women with recurrent ovarian cancer in platinum-sensitive and resistant, and PARP inhibitor resistant cohorts (e.g. Cohorts A, B, C, and D). Response to treatment will be measured according to RECIST 1.1 criteria. Complete response will be defined as the disappearance of all target lesions. All lymph nodes must be less than 10mm in short axis. Partial response will be defined as a 30% decrease in the sum of the diameters of the target lesions. Stable disease will be defined as a change in sum of the diameters that does not meet criteria for progressive disease or partial response.
The target DLT (dose level toxicity) rate for the MTD (maximum tolerated dose) is set at 30% and two alternatives; the highest DLT rate that deemed as sub-therapeutic is 25% and the lowest DLT rate that deemed as overly toxic is 35%.
| Arm | Type | Description |
|---|---|---|
| A. Olaparib Pill + AZD6738. | EXPERIMENTAL | Cohort A: Recurrent platinum-sensitive ovarian cancer (progression greater than 6 months from last receipt of platinum-based chemotherapy), approximately 37 patients could be treated with an interim analysis after 17 subjects. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water. |
| B. Olaparib Pill + AZD6738. | EXPERIMENTAL | Cohort B: Recurrent platinum-resistant ovarian cancer (progression less than or equal to 6 months of the last receipt), approximately 37 patients could be treated with an interim analysis after 12 subjects. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water. |
| C. Olaparib Pill + AZD6738. | EXPERIMENTAL | Cohort C: PARP inhibitor (PARPi) resistant (subjects who have progressed on a PARPi), patients must be platinum-sensitive, and have a germline or somatic BRCA mutation or an HRD mutation. Approximately 12 subjects could be treated. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water. |
| D-1. Olaparib Pill + AZD6738. | EXPERIMENTAL | Cohort D Part I: Patients will be platinum sensitive/platinum resistant ovarian cancer. Patient may or may not have received prior PARPi and will be enrolled irrespective of their BRCA status. The number of subjects treated will depend on the number of dose levels explored with a minimum of 12 subjects up to 30 subjects. All patients will receive the combination of AZD6738 and olaparib. Cohort D will take a lower dose of olaparib (100-200 mg daily for a 28-day cycle) and a higher dose of AZD6738 (160-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated. |
| D-2 Olaparib Pill + AZD6738. | EXPERIMENTAL | Cohort D Part II: Patients with ovarian cancer who are PARP inhibitor (PARPi) resistant (patients who have progressed on a PARPi). Patients must be platinum-sensitive and have a germline or somatic BRCA mutation or an HRD mutation. Approximately 12 patients will be treated. All patients will receive the combination of AZD6738 and olaparib. Cohort D will take a lower dose of olaparib (100-200 mg daily for a 28-day cycle) and a higher dose of AZD6738 (160-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated. |
| Name | Type | Description |
|---|---|---|
| Olaparib Pill | DRUG | For Cohorts A, B, and C: 300 mg twice daily by mouth which is taken continuously for 28 days, which is one cycle. Cohort D 1-2: prescribed lower dose of olaparib (100-200mg daily for a 28-day cycle). Three to five dosing schedules will be evaluated. Dose Levels 1-3: olaparib 100 mg twice daily, Days 1-28. For Dose Levels 4-5: 100-200 mg twice daily, Days 1-28. Other dose levels may be considered and will not exceed AZD6738 160mg twice daily by mouth and olaparib 150mg twice daily by mouth. |
| AZD6738 | DRUG | For Cohorts A, B, and C: 160 mg orally once daily for first 7 days of every cycle (Days 1-7 of each 28-day cycle). Cohort D 1-2: Prescribed higher dose of AZD6738 (120-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated. Dose Levels 1-3: 120-160 mg twice daily, Days 1-14, in combination with olaparib twice daily, Days 1-28. Alternatively, AZD6738 at 160 mg once daily Days 1-14 with olaparib at 100-150 mg Days 1-28 may be evaluated. Dose Levels 4-5: Alternative dosing schedule of AZD6738 at 80-160 mg once or twice daily, weekly intermittent schedule (Days 1-5, 8-12, 15-19) in combination with olaparib 100-200 mg twice daily, Days 1-28 may be evaluated. AZD6738 at 160 mg twice daily, Days 1-7 or 240 mg once daily Days 1-14 with olaparib 100-200 mg twice daily Days 1-28 may be evaluated. Other dose levels may be considered and will not exceed AZD6738 160mg twice daily by mouth and olaparib 150mg twice daily by mouth. |
Inclusion criteria: For inclusion in the study, patients must fulfill the following criteria: 1. Patients ≥ 18 years of age 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 6 months. 3. For Cohorts A-C, and Cohort D, Part II, patients must...