ceralasertib (AZD6738) / AstraZeneca - LARVOL DELTA

Safety and Efficacy of Ceralasertib plus Olaparib for Advanced/Metastatic Triple-Negative Breast Cancer in Three Molecular Strata: The Phase II VIOLETTE Study. (PubMed, Clin Cancer Res) - P2 | "In patients with advanced PARP inhibitor-naïve non-HRRm TNBC, ceralasertib + olaparib significantly improved ORR versus olaparib. However, clinical significance is limited without improvement in PFS."

Journal • P2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HRD

MONETTE: A Randomized Phase II Study of Ceralasertib plus Durvalumab or Ceralasertib Monotherapy in Patients with Advanced Melanoma Resistant to PD-(L)1 Inhibition. (PubMed, Clin Cancer Res) - "Both ceralasertib plus durvalumab and ceralasertib monotherapy demonstrated low response rates in anti-PD-(L)1-resistant advanced melanoma."

IO biomarker • Journal • Monotherapy • P2 data • Melanoma • Oncology • Solid Tumor • CD14 • CD8 • GDF15

Multicenter Phase II Study of Olaparib and the ATR Inhibitor Ceralasertib in Metastatic Castration-Resistant Prostate Cancer (TRAP). (PubMed, JCO Precis Oncol) - "Combining ceralasertib with olaparib had limited activity in patients with HRP mCRPC. HRRm response rate was not greater than previous single-agent PARP inhibitor clinical trials."

Journal • P2 data • Ataxia • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Disorders • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • HRD

Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-sensitive epithelial ovarian cancer (cohort A). (ASCO 2024) - P2 | "C+O was well tolerated and active in pts with platinum sensitive HGSOC warranting further evaluation. Efficacy was seen regardless of the presence of tumor genomic instability."

Clinical • P2 data • Anemia • Ataxia • Fatigue • Hematological Disorders • Immunology • Movement Disorders • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Primary Immunodeficiency • Solid Tumor • Thrombocytopenia • ATR • BRCA2 • BRIP1 • HRD • RAD51C

Ceralasertib plus durvalumab in Ras mutant and Ras wild type advanced non-small cell lung cancer: Two cohorts of the phase II platform National Lung Matrix Trial. (PubMed, Clin Cancer Res) - "Whilst outcome measures on ceralasertib/durvalumab in anti-PD-(L)1 resistant LUAD patients are modestly higher in KRAS mutant participants, these differences are not significant, a result likely related to the modest impact of KRAS mutation alone on the immunobiology of LUAD."

Journal • P2 data • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KEAP1 • KRAS • RAS • STAT1 • STK11

Phase I, dose-escalation study evaluating safety & efficacy of trastuzumab deruxtecan (T-DXd) in combination with ATR inhibitor (AZD6738, ceralasertib) in advanced solid tumors with HER2 expression (DASH) (ESMO 2025) - P1 | "Table: 939P Dose Level 1 (N = 6) 2 (N = 6) 3 (N = 6) 4 (N = 4) Total HER2 IHC 1/2+ (N = 15) 1/6 (17) 1/4 (25) 2/3 (67) 0/2 (0) 4/15 (27) 3+ (N = 7) - 1/2 (50) 2/3 (67) 1/2 (50) 4/7 (57) Total (N = 22) 1/6 (17) 2/6 (33) 4/6 (67) 1/4 (25) 8/22 (36) Table shows investigator-assessed objective response rate (%) per RECISTv1.1 Conclusions Preliminary evidence in this study showed that AZD6738 at 120 mg/d plus T-DXd at 5.4mg/kg was well-tolerated and yielded promising antitumor activity in heavily pretreated pts with high and low HER2-expressing advanced solid tumors. Expansion (colorectal and gastric-esophageal cancers) is ongoing and experience in other solid tumors is warranted."

Clinical • Combination therapy • Metastases • Esophageal Cancer • Gastric Cancer • Oncology • Solid Tumor • HER-2

Ceralasertib (C) + durvalumab (D) in patients (pts) with locally advanced (LA) or metastatic (m) NSCLC who progressed on or after anti-PD-(L)1 and platinum-based chemotherapy (CT): Results from LATIFY (ELCC 2026) - P3 | "Clinical trial identification NCT05450692. Conclusions C+D did not demonstrate a statistically significant improvement in OS vs docetaxel. C+D had manageable toxicity and AEs were consistent with the known safety profiles of each agent."

Clinical • Late-breaking abstract • Metastases • Lung Cancer • Non Small Cell Lung Cancer

An Update on the CONCORDE study: A Phase Ib Platform Study of DNA Damage Repair Inhibitors (DDRis) in Combination With Conventional Radiotherapy in NSCLC (BTOG 2025) - P1 | "In 2 study arms, participants also receive consolidation durvalumab ±DDRi for up to 12 months...The primary objective is to assess safety and to determine the recommended phase II dose of each DDRi. Since 17/03/21, 4 arms have opened: A (olaparib, PARPi), B (AZD1390, ATMi), C (ceralasertib, ATRi) and E (saruparib, PARP-1i)... CONCORDE continues to recruit patients to three study arms (A,C,E). The platform demonstrated excellent capability in identifying excess toxicity in DDRi-RT combinations, leading to Arm–B closure. Analysis of patient-reported outcomes and efficacy are ongoing."

Combination therapy • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PARP1

Resolution and Quantitation of Ribonucleosides and Deoxyribonucleosides in Digested Genomic DNA by UHPLC-MS/MS. (PubMed, Biomed Chromatogr) - "Ceralasertib (AZD6738) is the most clinically advanced ATR inhibitor (ATRi) and may abrogate this regulatory pathway and diminish RNR-mediated deoxynucleotide triphosphate synthesis...The method proved to be accurate (90.8%-114.2%) and precise (< 7.73% CV) across analytes. Freeze-thaw stability (106.4%-114.3%), stability for 12 months at -80°C (88.7%-113.7%), and stability for 4 h at room temperature (104.1%-114.0%) were acceptable across QCs."

Journal • Ataxia • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency

An update on the CONCORDE study: A phase Ib platform study of DNA damage repair inhibitors (DDRIs) in combination with conventional radiotherapy in NSCLC (ELCC 2025) - P1 | "Recruitment update: Since 17/03/21, 4 arms have opened: A (olaparib, PARPi), B (AZD1390, ATMi), C (ceralasertib, ATRi) and E (saruparib, PARP-1i)...DDRIs have been successfully escalated to dose level 2 (C + E) or 3 (A) with integration of consolidation durvalumab in 2 arms (C + E)...Analysis of patient-reported outcomes and efficacy are ongoing. A multimodality translational program to identify toxicity biomarkers is in development."

Combination therapy • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PARP1

VIOLETTE: Randomised Phase 2 Study of Olaparib (ola) + Ceralasertib (cer) or Adavosertib (ada) vs Ola Alone in Patients (pts) With Metastatic Triple-Negative Breast Cancer (mTNBC) (ESMO-BC 2022) - P2 | "Cer+ola had a manageable safety profile consistent with known profiles of each. Further analyses may identify pts likely to benefit from each treatment."

Clinical • P2 data • Anemia • Breast Cancer • Hematological Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • HRD

LATIFY: Phase 3 study of ceralasertib + durvalumab vs docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer that progressed on or after anti-PD-(L)1 and platinum-based therapy. (ASCO 2023) - P3 | "Approximately 580 pts will be recruited from around 21 countries in the Americas, Europe, and Asia Pacific. Clinical trial information: NCT05450692."

Clinical • Metastases • P3 data • Ataxia • Immunology • Lung Cancer • Movement Disorders • Non Small Cell Lung Cancer • Oncology • Primary Immunodeficiency • Solid Tumor • ALK • EGFR

Precision immuno-oncology for advanced non-small cell lung cancer (NSCLC) patients with PD-(L)1 inhibitors resistance (PIONeeR): A phase Ib/IIa clinical trial targeting identified resistance pathways (ESMO 2024) - P2 | "Pts were randomly allocated to Arm A: Durvalumab (Du) + Monalizumab, Arm B: Du + Oleclumab, Arm C: Du + Ceralasertib, Arm E: Du + Savolitinib or Arm D (control): Docetaxel. With its innovative and adaptive design, the PIONeeR trial was able to explore several options to overcome resistance to ICIs. Although no experimental arm performed better than outcomes observed with docetaxel, some pts had long DoR, suggesting durvalumab combinations can be highly effective. Biomarker work is ongoing to identify patients most likely to benefit from combination treatment."

Clinical • Immuno-oncology • IO biomarker • Late-breaking abstract • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Targeted therapy for DNA damage response and homologous recombination repair defects: The Olaparib Combinations trial. (PubMed, Cancer) - "The study failed to meet its primary end point of ORR. DDR and homologous recombination repair defects are not consistently actionable with olaparib as monotherapy or in combination with other targeted therapies in a histology-agnostic manner."

Journal • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • ARID1A • HRD

Publisher Correction: Ceralasertib Plus Durvalumab in Chinese Patients with Advanced Solid Tumors: A Nonrandomized Clinical Trial. (PubMed, Oncol Ther) - No abstract available

Clinical • Oncology • Solid Tumor

Experience pooling control arms within a complex phase I drug-radiotherapy (RT) platform trial (ESMO-TAT 2024) - P1 | "Table: 77P Treatment within each study arm Study arm 6 week RT period 1 year consolidation period CONCORDE-A Olaparib+RT No treatment RT only CONCORDE-B AZD1390+RT RT only CONCORDE-C Ceralasertib+RT Cerelasertib + durvalumab RT only Durvalumab CONCORDE-E AZD5305+RT Durvalumab RT only Results CONCORDE opened to recruitment in April 2021. Conclusions Pooling RT only patients across arms to estimate DLT rates presents a useful concurrent comparator to put the estimated DLT rate for informing dose escalation into context, and the rate in RT+DDRi patients to help attribute toxicity to the combination of DDRi and thoracic RT. The platform design necessitates fewer comparator patients, compared with multiple standalone comparison design trials."

P1 data • Lung Cancer • Oncology • Solid Tumor

Chemo-immunotherapy followed by durvalumab and ceralasertib in treatment naïve patients with extensive-stage small cell lung cancer (ESMO 2025) - P2 | "Methods A multicenter single arm phase II study was conducted to evaluate the efficacy of adding ceralasertib to maintenance durvalumab (CD) after induction with platinum-etoposide and durvalumab (PED) in patients with treatment naïve ES-SCLC. Fourteen patients (46.7%) developed serious adverse events, of which seven (50%) were treatment related. Conclusions The combination of chemo-immunotherapy followed by ceralasertib and durvalumab has shown promising efficacy with higher rates of 12- and 24-month survival over that expected for durvalumab maintenance alone, and did not show any new safety signal."

Clinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

CONCORDE: a phase Ib platform study of novel agents in combination with conventional radiotherapy in NSCLC (BTOG 2023) - "The primary objective is to assess safety and determine the recommended phase II dose of each DDRi+RT combination. As of 06/01/2023, CONCORDE-A (olaparib) and CONCORDE-B (AZD1390) are open to recruitment across 9 centres. The trial continues to recruit and CONCORDE-C (RT±ceralasertib with consolidation durvalumab±ceralasertib) has been approved and is due to open in January 2023. Two further study arms are planned. A parallel multimodality translational program to identify biomarkers of treatment response, toxicity and the impact on the immune system are in development."

Combination therapy • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

HUDSON: An Open-Label, Multi-Drug, Biomarker-Directed Phase 2 Study in NSCLC Patients Who Progressed on Anti-PD-(L)1 Therapy (IASLC-WCLC 2022) - P2 | "Here we present mature efficacy and safety results for the initial combinations - durvalumab plus: olaparib (PARP inhibitor; Module 1), danvatirsen (STAT3 inhibitor; Module 2), ceralasertib (ATR inhibitor; Module 3), and oleclumab (anti-CD73 antibody; Module 5). Durvalumab plus ceralasertib demonstrated a promising efficacy signal, with a tolerable safety profile, in patients with advanced/metastatic NSCLC following failure of anti-PD-1/PD-L1-containing immunotherapy and ≥1 platinum-doublet regimen."

Biomarker • Clinical • IO biomarker • P2 data • Anemia • Fatigue • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

The Prognostic and Predictive Impact of Circulating Tumour DNA Levels in Patients with Advanced Breast Cancer Enrolled on the plasmaMATCH Trial. (PubMed, Clin Cancer Res) - "Baseline low ctDNA levels predict response to targeted therapy, potentially suggesting shared mechanisms between high ctDNA release and resistance to therapy. Both baseline ctDNA levels and on-treatment dynamics are a promising surrogate endpoint for drug development, with clearance of ctDNA being a robust cross-therapy surrogate for outcome."

Circulating tumor DNA • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2 • PALB2

RAD51C breast cancer-identified variants with attenuated homologous recombination function exhibit sensitivity to combined PARP1 and ATR inhibition. (PubMed, NAR Cancer) - "While RAD51C variants with attenuated HR are largely resistant to monotherapy, cells expressing a subset of these RAD51C variants exhibit increased sensitivity to combination PARP1i and ATRi treatment, Saruparib and Ceralasertib, respectively. Collectively, we pinpoint the key functional regions of RAD51C and uncover a new C-terminal region proximal to the ATP-binding site in the folded RAD51C structure. Together, our findings suggest that variants with partial HR function can cause profound defects in the repair of replicative damage, and that this, in turn, may lead to distinct therapeutic responses."

Journal • Breast Cancer • Oncology • Solid Tumor • RAD51C

Results from plasmaMATCH trial cohort E: A phase II trial of olaparib and ceralasertib in patients with triple-negative advanced breast cancer (CRUK/15/010). (ASCO 2022) - "The response rate to olaparib and ceralasertib did not meet pre-specified criteria for efficacy in the overall evaluable population. Responses were observed in patients without germline or somatic BRCA1/2 mutations. Translational analyses are underway to identify potential biomarkers of response in this population and will be presented at the meeting."

Clinical • P2 data • Anemia • Breast Cancer • Hematological Disorders • Hypertension • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2

An Update on the CONCORDE study: A Phase Ib Platform Study of Novel Agents in Combination With Conventional Radiotherapy in NSCLC (IASLC-WCLC 2023) - P1 | "The primary objective is to assess safety and determine the recommended phase II dose of each DDRi+RT combination. As of 23/03/2023, CONCORDE-A (olaparib), CONCORDE-B (AZD1390) and CONCORDE-C (ceralasertib with consolidation durvalumab) are open to recruitment across 9 centres. The trial continues to recruit and CONCORDE-E (RT+/-AZD5305 with consolidation durvalumab) has been submitted and is due to open in May 2023. One further study arm is planned (CONCORDE-F). A parallel multimodality translational program to identify biomarkers of treatment response, toxicity and the impact on the immune system are in development."

Combination therapy • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Human ADME Study of [14C]-Ceralasertib (AZD6738) and Absolute Bioavailability of Ceralasertib (clinicaltrials.gov) - P1 | N=2 | Terminated | Sponsor: AstraZeneca | Not yet recruiting ➔ Terminated; A decision, based solely on business strategy, was taken to terminate study D533BC00002 on 22 December 2025, as the clinical development programme for ceralasertib has been discontinued.

Trial termination • Oncology • Solid Tumor

Phase II study of ceralasertib (ATR inhibitor) plus durvalumab in patients with advanced gastric cancer (AGC) who progressed on prior anti-PD-(L)1 therapy. (ASCO 2026) - P2 | "Ceralasertib plus durvalumab is efficacious and well-tolerated in IO-refractory AGC. The higher efficacy observed in patients treated immediately after prior IO failure suggests that ATR inhibition may effectively reverse acquired resistance to PD-1 blockade. This biomarker-driven approach warrants further validation in a larger cohort."

Clinical • IO biomarker • Metastases • P2 data • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • CHEK2 • HER-2