Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Administration of ceralasertib · 1 trial · 1 indication
Number of patients with adverse events and with serious adverse events including abnormal clinical observations, DLT, abnormal Electrocardiogram (ECG) parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline.
Intensive PK sampling at defined timepoints to measure Geometric mean and 90% CI for the ratio of fed: fasted in area under the plasma concentration time curve from zero to the last measurable time point (AUC0-t), area under the plasma concentration time curve from zero to infinity (AUC)
Change from baseline HR, PR, QRS and QTcF (ΔHR, ΔPR, ΔQRS and ΔQTcF) Categorical outliers for QTcF, HR, PR, and QRS Frequency of treatment emergent T and U wave abnormalities If a substantial HR effect is observed (i.e., the absolute value of the largest least squares \[LS\] mean ΔHR is greater than 10bpm in the by-time point analysis), other correction methods such as individualised and optimised individualised HR corrected QT interval (QTcI) will be explored and compared. The method that removes the HR dependence of the QT interval most efficiently will be chosen as the primary correction method.
| Arm | Type | Description |
|---|---|---|
| Module 2 Part A1 | EXPERIMENTAL | Module 2 Part A1: ascending doses of ceralasertib will be administered alone to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD) to take into Module 2 Part A2. |
| Module 2 Part A2 | EXPERIMENTAL | Module 2 Part A2: ascending doses of ceralasertib will be administered in combination with olaparib to patients to define the dose, frequency and schedule of ceralasertib and olaparib to take into Module 2 Part B. |
| Module 2 Part B1 | EXPERIMENTAL | Module 2 Part B1: Patients with second line 'ATM deficient' gastric adenocarcinoma including GEJ adenocarcinoma will receive ceralasertib with olaparib, at dose, frequency and schedule recommended from Module 2 Part A2. |
| Module 2 Part B2 | EXPERIMENTAL | Module 2 part B2: Patients with second line 'ATM proficient' gastric adenocarcinoma including GEJ adenocarcinoma will receive ceralasertib with olaparib, at dose, frequency and schedule recommended from Module 2 Part A2. |
| Module 2 Part B3 | EXPERIMENTAL | Module 2 Part B3: Patient with second or third line breast cancer with BRCA mutations (somatic or germline), excluding HER2 positive breast cancer will receive ceralasertib with olaparib, at dose, frequency and schedule recommended from Module 2 Part A2. |
| Module 2 Part B4 | EXPERIMENTAL | Module Part B4: Patients with second or third line triple negative breast cancer with no known BRCA mutations. This expansion will be enriched for patients with disease harbouring a HRR-related gene mutation (HRRm) will receive ceralasertib with olaparib, at dose, frequency and schedule recommended from Module 2 Part A2. |
| Module 3 Part A | EXPERIMENTAL | Module 3 Part A: cohort escalation of ceralasertib in combination with durvalumab in HNSCC or NSCLC patients to define the dose, frequency and schedule of ceralasertib and durvalumab to take into Module 3 Part B. Additionally, Module 3 Part A will include a serial tumour biopsy cohort to evaluate the Proof of Mechanism of ceralasertib in HNSCC and NSCLC patients. |
| Module 3 Part B | EXPERIMENTAL | Module 3 Part B: cohort expansions of ceralasertib in combination with durvalumab in HNSCC or NSCLC patients at dose, frequency and schedule from Module 3 Part A. |
| Module 2 Part B5 | EXPERIMENTAL | Patients with BRCA mutant or RAD51C/D mutant (either germline or somatic) or HRD-positive status epithelial ovarian, fallopian tube, or primary peritoneal cancer according to local testing. Patients must be platinum sensitive and previously progressed on a licensed PARPi. The cohort will be split into 2 groups: Cohort 1 - without intervening chemotherapy following progression on a PARPi, Cohort 2 - with intervening chemotherapy following progression on a PARPi. Patients will receive ceralasertib and olaparib, at the RP2D dose, frequency and schedule established from Module 2 Part A2. |
| Module 4 (FE/QT) | EXPERIMENTAL | Ceralasertib monotherapy will be administered on a number of days during Cycle 0 to assess the effect of food on ceralasertib absorption and effect of ceralasertib on ECG parameters under various conditions (fasted, fed, steady state). From C1 onwards, patients who participated in C0 will be allocated to either ceralasertib in combination with olaparib or durvalumab, or ceralasertib monotherapy and assessed for safety. |
| Module 5 Part A | EXPERIMENTAL | Module 5 Part A: ascending doses of ceralasertib will be administered in combination with AZD5305 to patients to define the MTD, RP2D. In case this first dose level is not tolerated, alternative schedules will be evaluated. |
| Module 5 Part B | EXPERIMENTAL | Module 5 Part B: cohort expansions of ceralasertib in combination with AZD5305 in ovarian patients at dose, frequency and schedule from Module 5 Part A. |
| Module 1 Part A | EXPERIMENTAL | Module 1 Part A: ascending doses of ceralasertib in combination with carboplatin AUC5 will be administered to patients to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD). |
| Module 1 Part B | EXPERIMENTAL | Module 1 Part B: patients with advanced lung adenocarcinoma with low expression of ATM will receive ceralasertib and carboplatin, at the dose, frequency and schedule recommended from Module 1 Part A. |
| Name | Type | Description |
|---|---|---|
| Administration of ceralasertib | DRUG | An oral formulation of ceralasertib will be used. In Module 2 Part A1, patients will receive a single dose of ceralasertib on Day 1, followed by 4 to 6 days washout, before multiple dosing. |
| Administration of ceralasertib in combination with olaparib | DRUG | An oral formulations of ceralasertib and olaparib will be used. In Module 2 Part A2, patients will receive either a single or twice daily dose of ceralasertib followed by 4 to 6 days washout, before multiple dosing with ceralasertib and olaparib. In Module 2 Part B, patients will receive ceralasertib and olaparib at the dose, frequency and schedule recommended from Module 2 Part A2. Cycle 0 may be omitted at the discretion of the sponsor. |
| Administation of ceralasertib in combination with durvalumab | DRUG | An oral formulation of ceralasertib will be used. Durvalumab is given via IV infusion. In Module 3 Part A, patients will receive an initial single dose of ceralasertib on Day 1, followed by multiple dosing in combination with durvalumab. In Module 3 Serial Tumour Biopsy Extension and Part B expansion cohorts, patients will receive ceralasertib at the dose, frequency and schedule recommended from Module 3 Part A, in combination with durvalumab. |
| Administration of ceralasertib monotherapy | DRUG | Module 4 Part A and Module 4 Part B Cohort 3: During C0, patients will receive ceralasertib monotherapy orally once a day on 3 non-consecutive days and ceralasertib twice a day on 5 consecutive days. After the patients have completed C0 (Part A) they may transition to Module 4 Part B cohort 3 where they will continue to receive ceralasertib monotherapy |
| Administration of ceralasertib and olaparib | DRUG | Module 4 Part B Cohort 1: After completion of Part A (C0), the patient may transition to Part B and be allocated to receive ceralasertib in combination with olaparib as decided by the investigator. |
| Administration of ceralasertib and durvalumab | DRUG | Module 4 Part B Cohort 2: After completion of Part A (C0), the patient may transition to Part B and be allocated to receive ceralasertib in combination with durvalumab as decided by the investigator. |
| Administration of ceralasertib in combination with AZD5305 | DRUG | An oral formulations of ceralasertib and AZD5305 will be used. In Module 5 Part A, patients will receive a single dose of ceralasertib on cycle 0 Day 1 as per dose level cohort. In Module 5 Part B, patients will receive ceralasertib and AZD5305: C1 onwards (as per dose level cohort allocated). |
| Administration of ceralasertib in combination with carboplatin | DRUG | An oral formulation of ceralasertib will be used. In Module 1 Part A, patients will receive a single dose of ceralasertib on Day 1, followed by multiple dosing in combination with carboplatin. A maximum of 6 cycles (21 days per cycle) of treatment will be given. In Module 1 Part B, patients will receive ceralasertib and carboplatin at the dose, frequency and schedule recommended from Module 1 Part A. |
Principal Inclusion criteria: * Aged at least 18 * The presence of a solid malignant tumour that is not considered appropriate for further standard treatment * Module 2 Part B study expansions, and Module 3: patients must have a tumour at least 1 cm in size that can be measured using a CT or MRI sc...
Ceralasertib is an investigational small molecule being developed by AstraZeneca PLC. It is currently in Phase 1 clinical development for the treatment of advanced solid malignancies, including head and neck squamous cell carcinoma, ATM proficient or deficient non-small cell lung cancer, gastric, breast, and ovarian cancer.
Ceralasertib is in Phase 1 clinical development. There is one active trial that is not recruiting participants. The trial is a controlled, open-label study, but it is not randomized or double-blinded.
The trial, NCT02264678, is a Phase 1 study titled 'Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents.' It is a controlled, open-label study with a planned enrollment of 358 participants. It is not randomized or double-blinded.
Ceralasertib is being studied for advanced solid malignancies, specifically head and neck squamous cell carcinoma, ATM proficient or deficient non-small cell lung cancer, gastric cancer, breast cancer, and ovarian cancer.
The trial enrolls adults aged 18 years and older of all sexes. Healthy volunteers are not eligible. The study is being conducted in the United States, France, South Korea, and the United Kingdom.
The clinical trial is evaluating ceralasertib in combination with chemotherapy and/or novel anti-cancer agents. The study involves ascending doses of ceralasertib given alongside these other treatments.