ceralasertib (AZD6738) / AstraZeneca - LARVOL DELTA

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 Legal entity responsible for the study AstraZeneca. 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

Testing the Addition of AZD6738 (Ceralasertib) to Immunotherapy to Increase Time Without Cancer for Patients With Non-Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=630 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Active, not recruiting

Checkpoint inhibition • Enrollment closed • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Combination of AVA-NP-695 and DDRi demonstrates strong synergy resulting in potent anti-tumor activity in rare pediatric cancers (AACR 2026) - "These findings underscore the therapeutic potential of AVA-NP-695 across hard-to-treat ICB-refractory pediatric cancers such as OS and EWS. AVA-NP-695 exploits ENPP1 inhibition to exert a strong anti-tumor response and obliviates metastasis. Additionally, AVA-NP-695 also demonstrates strong synergy with DDR inhibitors like Olaparib and Ceralasertib in both these cancers."

Clinical • Breast Cancer • Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Triple Negative Breast Cancer • ENPP1

Increased immune activity in patients with high-grade serious ovarian cancer after combination PARPi + ATRi therapy (AACR 2026) - "Characterizing the immune contexture of the tumor microenvironment and the surrounding stroma during treatment may provide valuable biological insights into the efficacy of this combination therapy and inform future combinations. Patients with recurrent HGSOC received ceralasertib 160mg orally daily, days 1-7 and olaparib 300mg twice daily, days 1-28 of a 28-day cycle. The increased immune cell densities measured by mIHC indicate overall activation of the immune system following PARPi + ATRi treatment. Elevated levels of PD-1⁺ and Granzyme B⁺ T cells suggest enhanced immune activation and cytotoxic potential, while comparative analysis of the tumor versus stroma compartments demonstrates improved immune cell infiltration into the tumor. Notably, higher baseline densities of M2-like macrophages may influence or limit response to therapy."

Clinical • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD8 • GZMB • PD-1

Combination of medroxyprogesterone acetate (MPA) and a WEE1 or ATR inhibitor enhances anti-tumor activity of estrogen receptor-positive endometrial cancer cells (AACR 2026) - "Tamoxifen, letrozole, fulvestrant, and medroxyprogesterone acetate (MPA, 25 μM for MFE280; 30 μM for ARK1) were used as hormone therapies. As drugs for targeted therapies, either the ATR inhibitor (ATRi) AZD6738 (2.5 μM) or the WEE1 inhibitor (WEE1i) MK1775 (0.1 μM) was employed... We found that the combination of MPA and ATRi markedly enhances anti-tumor activity in ER+ endometrial cancer, in an ERα expression-dependent manner. Future studies are needed to elucidate the mechanism of these synergistic effects."

IO biomarker • Breast Cancer • Endometrial Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AURKA • CCND1 • ER

Ataxia telangiectasia and Rad3 related kinase inhibitors and gemcitabine induce synergistic killing of uterine leiomyosarcoma cells (AACR 2026) - "Therefore, we investigated the potential for ATR inhibitors to enhance the potency and efficacy of chemotherapy for uLMS in vitro. CellTitre Glo, Bliss Independence analysis, and Multidimensional Synergy of Combinations (MuSyC) assessed synergy between three ATRi (elimusertib, ceralasertib, berzosertib) and SOC chemotherapy (gemcitabine, doxorubicin, docetaxel) in three commercially available (SK-LMS-1, SK-UT-1B, SK-UT-1) and two patient-derived uLMS cell lines (ACI-44A, ACI-44B). Elimusertib strongly synergizes with gemcitabine in vitro across uLMS cell lines by potentiating DNA damage and apoptosis. The lack of synergy with docetaxel or doxorubicin underscores gemcitabine as the most effective combination with ATR inhibitors. These finds support further preclinical and clinical evaluation of elimusertib + gemcitabine as a promising novel therapy for uterine leiomyosarcoma."

Gynecologic Cancers • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • Uterine Leiomyosarcoma • ANXA5 • ATR • CASP3 • CHEK1

Liposomal Vitamin C as a Modulator of the Efficacy of Ceralasertib Therapy in Ovarian Cancer. (PubMed, Int J Mol Sci) - "The formation of DNA double-strand breaks suggests replication fork collapse. Our findings demonstrates that this synthetic targeted therapy, combining a novel liposomal formulation of VitC with an ATR inhibitor, not only enhances DNA damage and the cytotoxic efficacy of ceralasertib but also effectively drives ovarian cancer cells toward cell death."

Journal • Ataxia • Immunology • Movement Disorders • Oncology • Ovarian Cancer • Primary Immunodeficiency • Solid Tumor • ACSL4

In-depth profiling of SCLC models of acquired chemoresistance reveals SLFN11-dependent antibody-drug conjugate payload sensitivity and ATR inhibitor synergy (AACR 2026) - "Drug screens were conducted to identify therapeutic vulnerabilities, including responses to unconjugated antibody-drug conjugate (ADC) payloads and targeted pathway inhibitors. Cisplatin-resistant (CR) SCLC models exhibited broad cross-resistance to clinically relevant cytotoxic drugs such as carboplatin, lurbinectedin, and topoisomerase I and II (TOP1 and TOP2) inhibitors...Importantly, inhibition of ATR with ceralasertib synergized with DNA-damaging ADC payloads, re-sensitizing SLFN11-low resistant models by increasing DNA damage and inducing apoptosis. Our findings demonstrate shared adaptive mechanisms of acquired cisplatin resistance in SCLC, including checkpoint rewiring and metabolic flexibility... Our findings demonstrate shared adaptive mechanisms of acquired cisplatin resistance in SCLC, including checkpoint rewiring and metabolic flexibility. SLFN11 was identified as a key determinant of TOP1-directed ADC efficacy. Combining ATR inhibition with DNA-damaging..."

ADC • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • SLFN11 • TOP1

Combination activity of T-DXd and dato-DXd with DNA damage response inhibitors (ESMO-TAT 2026) - "We profiled the activity of two TOP1i-charged ADCs (T-DXd, Dato-DXd), in combination with DDRi, targeted against ATM (AZD1390), ATR (ceralasertib), PARP (olaparib, saruparib) or WEE1 (adavosertib), using preclinical cancer models. Combinations of TOP1i-ADCs with selected DDR inhibitors and optimized dosing schedules, enhance therapeutic response and reduce toxicity, guiding ongoing and future clinical investigations."

Oncology • PARP1 • TOP1

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

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

Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial (clinicaltrials.gov) - P1 | N=51 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Mar 2026 ➔ Mar 2027

P53mut • Trial completion date • Trial primary completion date • Biliary Cancer • Breast Cancer • Carcinosarcoma • Colon Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Salivary Gland Cancer • Sarcoma • Solid Tumor • Uterine Cancer • CD4

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

ATR Blockade Potentiates the Effects of Genotoxic Agents In Vitro and Promotes Antitumor Immunity in a Mouse Model of Non-Small Cell Lung Cancer. (PubMed, Cancers (Basel)) - "These results demonstrate that ATR blockade concurrently enhances the efficacy of genotoxic agents and immune checkpoint inhibitors, thus paving the way for combination therapies in NSCLC."

IO biomarker • Journal • Preclinical • Ataxia • Immunology • Lung Cancer • Movement Disorders • Non Small Cell Lung Cancer • Oncology • Primary Immunodeficiency • Solid Tumor • CD4 • CD8

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

PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Assistance Publique Hopitaux De Marseille | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2023 ➔ Feb 2024 | Trial primary completion date: Mar 2023 ➔ Oct 2023

Enrollment open • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • ALK • EGFR • ROS1

PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Assistance Publique Hopitaux De Marseille

New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • ALK • EGFR • ROS1

PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov) - P2 | N=114 | Active, not recruiting | Sponsor: Assistance Publique Hopitaux De Marseille | Recruiting ➔ Active, not recruiting | Trial completion date: Feb 2024 ➔ Feb 2025 | Trial primary completion date: Oct 2023 ➔ Oct 2024

Enrollment closed • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=531 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Sep 2024 ➔ Sep 2026 | Trial primary completion date: Sep 2024 ➔ Sep 2026

Biomarker • IO biomarker • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=320 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jul 2021 ➔ Sep 2022 | Trial primary completion date: Jul 2021 ➔ Sep 2022

Biomarker • IO biomarker • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov) - P1/2 | N=250 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Apr 2021 ➔ Sep 2021 | Trial primary completion date: Apr 2021 ➔ Sep 2021

Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Triple Negative Breast Cancer • ATM • BRCA • HER-2 • HRD • RAD51C • RAD51D

D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov) - P1/2 | N=117 | Recruiting | Sponsor: AstraZeneca | N=322 ➔ 117 | Trial completion date: Jan 2022 ➔ May 2022 | Trial primary completion date: Jan 2022 ➔ May 2022

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ATM • BRCA • HER-2 • HRD • RAD51C • RAD51D

D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov) - P1 | N=114 | Recruiting | Sponsor: AstraZeneca | Phase classification: P1/2 ➔ P1

Phase classification • Breast Cancer • Colorectal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ATM • BRCA • HER-2 • HRD • RAD51C • RAD51D

D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov) - P1/2 | N=250 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Apr 2021 ➔ Aug 2019

Trial primary completion date • Breast Cancer • Colorectal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Triple Negative Breast Cancer • ATM • BRCA • HER-2 • HRD • RAD51C • RAD51D

D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov) - P1/2 | N=250 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Nov 2019 ➔ Apr 2020 | Trial primary completion date: Oct 2018 ➔ Aug 2019

Trial completion date • Trial primary completion date • Colorectal Cancer • Gastric Adenocarcinoma • Gastric Cancer • HER2 Breast Cancer • Lung Adenocarcinoma • Non Small Cell Lung Cancer • Ovarian Cancer • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ATM • BRCA • HER-2 • HRD • RAD51C • RAD51D