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Ceralasertib

Phase 3

Advanced or Metastatic Non-Small Cell Lung Cancer | Small molecule | Oncology |AstraZeneca PLC|Last Updated: Jul 13, 2026

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Trial Design
RandomizedACTIVE_CONTROLLEDDMC
Total Trials1
Total Enrollment594
FDA Designations
No designations recorded
Clinical trial landscape

Ceralasertib · 9 trials · 8 indications

Phase 3 1Phase 2 5Phase 1 3
NCT05450692A Phase III Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Non Small Cell Lung Cancer (NSCLC) Whose Disease Progressed On or After Prior Anti PD (L)1 Therapy And Platinum Based ChemotherapyAdvanced or Metastatic Non-Small Cell Lung Cancer
ACTIVE NOT_RECRUITING594 Analytics
PHASE3ACTIVE NOT_RECRUITING
A Phase III Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Non Small Cell Lung Cancer (NSCLC) Whose Disease Progressed On or After Prior Anti PD (L)1 Therapy And Platinum Based Chemotherapy
Advanced or Metastatic Non-Small Cell Lung CancerUnlock trial analytics
Study Endpoints
Primary Endpoints
Overall Survival (OS)
Every 3 months (± 1 week) following objective progression of disease (PD) or treatment discontinuation (up to three years)

The superiority of ceralasertib plus durvalumab combination therapy relative to docetaxel will be demonstrated by assessment of OS (HR with 95% CI and p-value) in participants with advanced NSCLC after second- or third-line therapy and without actionable genomic alterations. OS is defined as time from randomisation until the date of death due to any cause.

Objective response rate (ORR)
At month 6 after the last patient's first dose (approximately 18 months).

Objective response rate (ORR) is defined as the proportion of participants who have a complete response (CR) or partial response (PR) per RECIST 1.1.

Progression free survival (PFS)
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

ATRiBRAVE will evaluate the efficacy of ceralasertib followed by durvalumab plus nab-paclitaxel in patients with TNBC, whose tumor relapsed following treatment with curative intent for early disease, which must have included ICIs and chemotherapy as part of the radical locoregional therapy (either adjuvant, neoadjuvant or both).

Main Study: Objective Response Rate (ORR)
Cycle 1 Day 1 (Each Cycle is 28 days) until objective disease progression or the last evaluable assessment in the absence of progression, or data cut-off (1 year 8 months)

ORR was defined as the proportion of participants who had a complete response (CR) or partial response (PR) prior to any evidence of progression (as defined by Response Evaluation Criteria in Solid Tumours \[RECIST\] 1.1) that is confirmed at least 4 weeks later. As per planned in protocol, this outcome measure was assessed only for main study.

Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-area in the Center Tumor Region
Baseline, On-treatment (Cycle 0 Day 7), and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

Changes in CD8+ T-cell infiltration of tumours induced by ceralasertib monotherapy was assessed in baseline, on-treatment and off-treatment tumour biopsies As per planned in protocol, this outcome measure was assessed only for biopsy study.

Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-area in the Invasive Margin Region
Baseline, Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

Changes in CD8+ T-cell infiltration of tumours induced by ceralasertib monotherapy was assessed in baseline and off-treatment tumour biopsies As per planned in protocol, this outcome measure was assessed only for biopsy study.

Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Center Tumor Region
Baseline, On-treatment (Cycle 0 Day 7), and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

Changes in CD8+ T-cell infiltration of tumours induced by ceralasertib monotherapy was assessed in baseline, on-treatment and off-treatment tumour biopsies As per planned in protocol, this outcome measure was assessed only for biopsy study.

Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Invasive Margin Region
Baseline, and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

Changes in CD8+ T-cell infiltration of tumours induced by ceralasertib monotherapy was assessed in baseline and off-treatment tumour biopsies As per planned in protocol, this outcome measure was assessed only for biopsy study.

Cohort A (aST): Objective Response Rate (ORR).
2 years 4 months

ORR is defined as the percentage of participants who have at least one response of complete response (CR) or partial response (PR) prior to any evidence of progression (as defined by response evaluation criteria in solid tumours \[RECIST\] 1.1) that is confirmed at least 4 weeks later. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.

Cohort B (mCRPC): Composite Response Rate.
Up to 2 years 4 months

Composite response rate is defined as the investigator assessed radiological response by RECIST 1.1 for soft tissue and visceral lesions and Prostate Cancer Working Group 3 (PCWG3) for bone lesions, confirmed prostate specific antigen (PSA) decline of more than 50%, and/or confirmed circulating tumour cell \[CTC\] conversion from unfavorable (\>=5 cells/7.5 ml blood) to favorable (\<5 cells). Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.

Confirmed overall objective response rate (complete or partial response) as defined by RECIST version 1.1.
From start of treatment until treatment discontinuation - minimum follow-up of 16 weeks (if not progressed earlier), up to max study period (estimated 36 months).

A patient will be said to have had an overall objective response if they have a complete/partial response as assessed radiologically according to RECIST 1.1 at any point during trial treatment. A second scan to confirm response will be taken ≥ 4 weeks after the first scan showing an objective response.

The number of subjects with dose-limiting toxicity, as defined in the protocol.
From the first dose of study treatment Up to and including the end of cycle 1(each cycle is 28 days) .

Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optional therapeutic intervention, meets protocol-defined criteria.

Safety and tolerability in terms of adverse events
From the first dose of study treatment until 28 days after the last dose.

Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters

Conversion of an immunologically based 25-gene signature from a prognostically unfavourable state to a prognostically favourable state.
From baseline through Day 31 (Follow up)

To investigate prognosis-correlated immune activation due to DDR inhibition by monitoring the induction of immunologically relevant genes in tumours of patients treated with study investigational agent(s)

Secondary Endpoints
Progression-Free Survival (PFS)
Up to 3 years
Objective Response Rate (ORR)
Up to 3 years
Duration of Response (DoR)
Up to 3 years
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Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Group A: Ceralasertib plus durvalumab combination therapyEXPERIMENTALParticipants will be administered ceralasertib orally followed by durvalumab administered intravenously.
Group B: Docetaxel monotherapyACTIVE_COMPARATORParticipants will be administered docetaxel (standard of care) administered intravenously.
Group AEXPERIMENTALCeralasertib plus durvalumab combination therapy Participants will be administered orally ceralasertib followed by IV durvalumab each 28 days cycle.
TNBC patients treated with ceralasertib, durvalumab e nab-paclitaxelEXPERIMENTALPatients will be assessed for eligibility during the 28-day screening period prior to enrollment. Enrolled patients will be treated with: * Ceralasertib at 240 mg administered orally, twice daily on Days -6 to 0 prior to Day 1 Cycle 1 and thereafter on Days 22 to 28 (priming period) of Cycle 1 and every subsequent cycle; * Durvalumab at 1500 mg administered via IV infusion on Day 1 of every 28-day cycle; Nab-paclitaxel at 100 mg/m2 administered via IV infusion on Days 1,8 and 15 of every 28- day cycle. A safety run-in phase will be carried out at the start of the present study using a 3+3 de-escalating schema down to -2 ceralasertib dose level. Nab- paclitaxel or durvalumab doses will not be de-escalated. Once the definitive dose for ceralasertib is established, treatment will be continued until progression or unacceptable toxicity, which ever come first.
Main study: Ceralasertib + DurvalumabEXPERIMENTALParticipants will receive ceralasertib on Days 1 to 7 plus durvalumab Day 8, once in 28 days (Q28D), until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion is met.
Main study: CeralasertibEXPERIMENTALParticipants will receive ceralasertib on Days 1 to 7, Q28D, until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion is met.
Biopsy Sub-study: Ceralasertib + DurvalumabEXPERIMENTALFrom Cycle 1, participants will receive combination of ceralasertib twice daily (BD) Days 1 to 7 plus durvalumab Day 8, Q28D, until progressive disease, unacceptable toxicity, withdrawal of consent, or a study treatment discontinuation criterion is met.
Biopsy study: CeralasertibEXPERIMENTALDuring Cycle 0, participants will receive ceralasertib on Days 1 to 7, followed by an off-treatment period between Days 8 to 28.
Cohort AEXPERIMENTALEligible participants (ATM altered AST), will receive oral dose of Ceralasertib as monotherapy.
Cohort BEXPERIMENTALEligible participants (ATM altered mCRPC), will receive oral dose of Ceralasertib as monotherapy.
1A: ceralasertib (AZD6738)EXPERIMENTALWomen with relapsed ovarian (fallopian tube / primary peritoneal) and endometrial (uterus) clear cell carcinomas with loss of ARID1A expression treated with single agent AZD6738.
1B: ceralasertib (AZD6738) + olaparibEXPERIMENTALIn second stage of trial, opening of this cohort depends on response rate in cohort 1A during first stage of trial. Women with relapsed ovarian (fallopian tube / primary peritoneal) and endometrial (uterus) clear cell carcinomas with loss of ARID1A expression treated with AZD6738 in combination with olaparib.
2: ceralasertib (AZD6738) + olaparibEXPERIMENTALWomen with relapsed ovarian (fallopian tube / primary peritoneal) and endometrial (uterus) clear cell carcinomas with NO loss of ARID1A expression treated with AZD6738 in combination with olaparib.
3: ceralasertib (AZD6738) + olaparibEXPERIMENTALWomen with other rare relapsed gynaecological cancers (endometrioid ovarian carcinoma, endometrioid endometrial carcinoma, cervical adenocarcinoma, cervical squamous, ovarian carcinosarcoma and endometrial carcinosarcoma) irrespective of ARID1A status, treated with AZD6738 in combination with olaparib.
4: ceralasertib (AZD6738) + durvalumabEXPERIMENTALWomen with endometrial cancers (serous, clear cell, endometroid, carcinosarcoma) with ARID1A loss.
5: ceralasertib (AZD6738) + durvalumabEXPERIMENTALWomen with endometrial cancers (serous, clear cell, endometroid, carcinosarcoma) with NO loss of ARID1A.
Ceralasertib in Combination with DurvalumabEXPERIMENTALThis is a sequential group treatment/dose-escalation study with 2 cohorts with no masking.
Ceralasertib monotherapyEXPERIMENTALThis is a sequential group treatment/dose-escalation study with 2 cohorts with no masking.
AZD6738EXPERIMENTALAZD6738 (160 mg) tablet twice daily continuous dosing for a minimum of 9 days and a maximum of 21 days.
OlaparibEXPERIMENTALOlaparib (300 mg) tablets administered orally twice daily continuously for a minimum of 9 days and a maximum of 21 days.
Interventions
NameTypeDescription
CeralasertibDRUGParticipants will receive ceralasertib oral tablets.
DurvalumabDRUGParticipants will receive durvalumab as an intravenous infusion.
DocetaxelDRUGParticipants will received docetaxel as an intravenous infusion.
Nab-paclitaxelDRUG100mg/m2 i.v. day 1,8,15 (q28)
OlaparibDRUGPARP inhibitor
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Eligibility Criteria
Age Range18 Years to 130 Years
SexALL
Healthy VolunteersNo
Study Sites191

Inclusion Criteria: * Histologically or cytologically documented NSCLC that is locally advanced or metastatic according to Version 8 of the IASLC Staging Manual in Thoracic Oncology. * Documented epidermal growth receptor factor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type status as determ...

Countries:United StatesArgentinaAustraliaBelgiumBrazilCanadaChinaFranceGermanyHong KongHungaryIndiaIrelandItalyJapanNetherlandsPolandRomaniaSerbiaSouth KoreaSpainTaiwanUnited KingdomRussia
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Competitive Landscape -Non-Small Cell Lung Cancer 395 trials (matched to "Advanced or Metastatic Non-Small Cell Lung Cancer")
Recent Changes (Last 90 Days)
LOWJul 13, 2026NCT05450692lastUpdatePostDate: changed
LOWJul 13, 2026NCT05450692lastUpdatePostDate: changed
LOWJun 18, 2026NCT05941897lastUpdatePostDate: changed
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MEDIUMMay 26, 2026NCT05450692primaryCompletionDate: changed
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LOWMay 24, 2026NCT05450692studyFirstPostDate: changed