Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AZD6738 and olaparib · 1 trial · 3 indications
Change in mean proliferation index (as measured by tumour cell Ki67 staining) post WOP intervention within post-treatment biopsy compared to pre-treatment baseline biopsy. A patient will be defined as being a Ki67 responder if they experience a relative decrease in Ki67 positive cells of ≥33% in the post-treatment biopsy sample. This represents a characterised threshold that we do not believe would be exceeded by chance in this patient population. AND/OR Cohorts B and C co-primary endpoint #2, as described below.
Changes in the proliferation gene expression signature post WOP intervention within the post-treatment biopsy compared to pre-treatment baseline biopsy. A patient will be defined as being a responder if there is a ≥1.5-fold drop in the proliferation gene expression in the surgical resection sample. The proliferation gene signature will be based on this list of 11 highly correlated proliferation genes shown in multiple studies including those published by The Cancer Genome Atlas and they also contribute to the calculation of the proliferation score in the publicly available PAM50 classifier. The list consists of :"CCNB1","UBE2C","BIRC5","NDC80","CDC20","PTTG1","RRM2","MKI67","TYMS","CEP55","NUF2" For each sample, a proliferation gene module score will be calculated according to the expression of the relevant genes. AND/OR Cohorts B and C co-primary endpoint #1, as described above.
Change in frequency of CD8+ sTILs post anti-PD-L1 immunotherapy within the post-treatment biopsy compared to pre-treatment baseline biopsy. A patient will be defined as being a responder if they experience an absolute increase of ≥ 10% in the percentage CD8+ sTILs within the post-treatment biopsy sample. The % CD8+ sTILs value denotes the area occupied by CD8+ sTILs over total intratumoural stromal area. AND/OR Cohort D co-primary endpoint #2, as described below.
Changes in the interferon gamma-positive (IFNγ+) signature post WOP intervention within the post-treatment biopsy compared to pre-treatment baseline biopsy. A patient will be defined as being a responder if there is a ≥2-fold increase in the IFNγ+ gene expression in the post-treatment biopsy sample.The four-gene IFNγ+ score will be calculated, comprising of IFNγ, CD274, LAG3, and CXCL9. AND/OR Cohort D co-primary endpoint #1, as described above.
Change in mean proliferation index (as measured by tumour cell Ki67 staining) post WOP intervention within the post-treatment biopsy compared to pre-treatment baseline biopsy. A patient will be defined as being a Ki67 responder if they experience a relative decrease in Ki67 positive cells of ≥33% in the post-treatment biopsy sample. This represents a characterised threshold that we do not believe would be exceeded by chance in this patient population. AND/OR Cohorts F and G co-primary endpoints #2 and #3, as described below
Changes in the proliferation gene expression signature post WOP intervention within the post-treatment biopsy compared to pre-treatment baseline biopsy. A patient will be defined as being a responder if there is a ≥1.5-fold drop in the proliferation gene expression in the post-treatment biopsy sample. The proliferation gene signature will be based on this list of 11 highly correlated proliferation genes shown in multiple studies including those published by The Cancer Genome Atlas and they also contribute to the calculation of the proliferation score in the publicly available PAM50 classifier. The list consists of : "CCNB1","UBE2C","BIRC5","NDC80","CDC20","PTTG1","RRM2","MKI67","TYMS","CEP55","NUF2" For each sample, a proliferation gene module score will be calculated according to the expression of the relevant genes. AND/OR Cohorts F and G co-primary endpoints #1 and #3, as described above, and below respectively
Changes in the plasma ctDNA (D0-D14) post WOP intervention compared to pre-treatment. A patient will be defined as being a responder if the ratio of ctDNA post-WOP compared to pre-WOP is \<0.25. This cut-off has been selected in line with other studies of PARP inhibitors in TNBC. AND/OR Cohorts F and G co-primary endpoints #1 and #2, as described above
| Arm | Type | Description |
|---|---|---|
| Cohort A (standard care reference cohort) | NO_INTERVENTION | Arm formally closed to recruitment since 06 August 2024 |
| Cohort B (AZD6738 monotherapy) | EXPERIMENTAL | Arm formally closed to recruitment since 06 August 2024 |
| Cohort C (olaparib monotherapy) | EXPERIMENTAL | Arm formally closed to recruitment since 06 August 2024 |
| Cohort D (durvalumab monotherapy) | EXPERIMENTAL | Arm formally closed to recruitment since 06 August 2024 |
| Cohort E: non-HRD and gBRCA1gBRCA1/2 wildtype confirmed at HRD screening | EXPERIMENTAL | - |
| Cohort F: gBRCA1/2 mutation confirmed at HRD screening | EXPERIMENTAL | - |
| Cohort G: HRD & gBRCA1/2 wildtype confirmed at HRD screening | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| AZD6738 | DRUG | PART 1: Pre-operative exposure of 160mg AZD6738 to be administered orally twice daily on Days 5 -14 of the WOP. PART 2: 12 months post-operative exposure to 160mg AZD6738 to be administered orally twice daily on Days 1 - 14 of a 28 day cycle. AZD6738 was removed as intervention under investigation as of 06 August 2024 (due to formal closure of cohort B) |
| Olaparib | DRUG | PART 1 (cohort C, and cohorts E-G): Pre-operative exposure to 300mg of olaparib to be administered orally twice daily on Days 1-14 of the WOP. PART 2 (cohort C, and cohorts F and G): 12 months post-operative exposure to 300mg olaparib (2 x 150mg tablets) to be administered orally twice daily on a continuous schedule Day 1-28 of a 28 day cycle. Cohort C was formally closed to recruitment since 06 August 2024. |
| Durvalumab | DRUG | PART 1 (cohort D): Pre-operative exposure to 1500mg durvalumab to be administered via intravenous (IV) infusion on Day 1 only of the WOP. PART 2 (cohorts A and D, and cohorts F and G): 12 months post-operative exposure to 1500mg durvalumab to be administered via intravenous (IV) infusion on Day 1 only of a 28 day cycle. Cohorts A and D were formally closed to recruitment since 06 August 2024. |
Inclusion Criteria for Trial Registration: 1. Signed Informed Consent Form (ICF) for Trial Registration; 2. Aged ≥18 years old; 3. Histologically confirmed invasive triple negative breast cancer (TNBC). TNBC defined as ER negative, PgR negative (ER and PgR negative as defined by Allred score 0/8, 1...
AZD6738, also known as ceralasertib, is an investigational small molecule being developed for the treatment of neoplasms, which are abnormal growths of tissue that can be benign or malignant. It is currently in Phase 1 clinical development for oncology indications.
AZD6738 is being developed by AstraZeneca PLC, a multinational pharmaceutical company. AstraZeneca's stock is traded under the ticker symbol AZN on major stock exchanges.
AZD6738 is currently in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The drug is being studied in early-stage clinical trials to evaluate its safety, tolerability, and pharmacokinetics in patients with neoplasms.
AZD6738 is being studied in a Phase 1 clinical trial with the identifier NCT06754761. The trial is titled 'Human ADME Study of [14C]-Ceralasertib (AZD6738) and Absolute Bioavailability of Ceralasertib' and was conducted in the United Kingdom. The study enrolled 2 participants with neoplasms.
Yes, AZD6738 is also known as ceralasertib. The drug is referred to by both names in clinical research and development contexts. The clinical trial NCT06754761 uses the name ceralasertib in its title, along with the AZD6738 designation.