MelanomaPhase 2MONETTENCT05061134
A Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Melanoma and Resistance to PD-(L)1 Inhibition
A Phase 2 study testing Ceralasertib and Durvalumab in people with Melanoma, run by AstraZeneca at 66 sites in 11 countries.
Trial summary
Main study: This is an open-label, phase 2 study that aims to evaluate the efficacy and safety/tolerability of ceralasertib, when administered as monotherapy and in combination with durvalumab in participants with unresectable or advanced melanoma and primary or secondary resistance to PD-(L)1 inhibition. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Melanoma
- What is being tested?
- Ceralasertib and Durvalumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 194 participants
- Where
- 66 sitesin 11 countries
- Study dates
- 11 Aug 2022to 2 Nov 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have a histologically or cytologically confirmed diagnosis of unresectable or metastatic melanoma of cutaneous, acral or mucosal subtype
- Availability of an archival tumour sample and a fresh tumour biopsy taken at screening
- Patient must have received at least 1 prior immunotherapy (anti-PD-(L)1 ± anti-CTLA-4 [Cytotoxic T-lymphocyte-associated protein 4]) for a minimum of 6 weeks and no more than 2 prior regimens in the metastatic setting. Patients must have confirmed progression during treatment with a PD-(L)1 inhibitor +/- a CTLA-4 inhibitor.
- The interval between the last dose of anti-PD-(L)1, BRAF/MEK (B-Rapidly Accelerated Fibrosarcoma gene/mitogen-activated protein kinase gene) inhibitor and the first dose of the study regimen must be a minimum of 14 days
- Measurable disease by RECIST 1.1.
- Patients must have a life expectancy ≥3 months from proposed first dose date.
- Biopsy Sub-study: Consent to the provision of 3 mandatory tumour biopsies.
Who cannot join
- Patients must not have experienced a toxicity that led to permanent discontinuation of prior checkpoint inhibitors (CPI) treatment.
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 3 years before the first dose of study treatment
- Uveal melanoma
- Must not have experienced a Grade ≥ 3 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy
- History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the study clinical lead.
- History of organ transplant that requires use of immunosuppressive medications
Show all 9Show fewer
- Inadequate bone marrow and impaired hepatic or renal function
- Known active infection requiring systemic therapy, active hepatitis infection, positive hepatitis C virus antibody, hepatitis B virus (HBV) surface antigen or HBV core antibody (anti-HBc), at screening
- Patients with confirmed COVID-19 infection by polymearse chain reaction test who have not made a full recovery.
Trial locations and contacts
66 sites in 11 countries.
66 sites in 11 countries
Germany10 sites
Research Site
Berlin, 10117
Research Site
Buxtehude, 21614
Research Site
Heidelberg, 69120
Research Site
Heilbronn, 74078
Research Site
Kiel, 24105
Research Site
Mainz, 55131
Research Site
München, 80337
Research Site
Regensburg, 93053
Research Site
Schwerin, 19049
Research Site
Tübingen, D-72076
France9 sites
Research Site
Bobigny, 93009
Research Site
Boulogne-Billancourt, 92100
Research Site
Marseille, 13385
Research Site
Paris, 75010
Research Site
Pau, 64046
Research Site
Pierre-Bénite, 69310
Research Site
Poitiers, 86021
Research Site
Vandœuvre-lès-Nancy, 54511
Research Site
Villejuif, 94805
Spain8 sites
Research Site
Barcelona, 08041
Research Site
Madrid, 28007
Research Site
Madrid, 28027
Research Site
Madrid, 28034
Research Site
Madrid, 28040
Research Site
Málaga, 29009
Research Site
Pamplona, 31008
Research Site
Pozuelo de Alarcón, 28223
Italy7 sites
Research Site
Candiolo, 10060
Research Site
Milan, 20141
Research Site
Naples, 80131
Research Site
Padova, 35128
Research Site
Perugia, 06156
Research Site
Roma, 00168
Research Site
Siena, 53100
United States6 sites
Research Site
Los Angeles, California, 90024
Research Site
Lutherville-Timonium, Maryland, 21093
Research Site
Nashville, Tennessee, 37232
Research Site
Sacramento, California, 95816
Research Site
San Francisco, California, 94143
Research Site
Tampa, Florida, 33612
Poland6 sites
Research Site
Brzozów, 36-200
Research Site
Gdansk, 80-214
Research Site
Krakow, 31-115
Research Site
Lodz, 93-513
Research Site
Poznan, 60-355
Research Site
Warsaw, 02-781
Australia4 sites
Research Site
Darlinghurst, 2010
Research Site
East Melbourne, 3002
Research Site
Herston, 4029
Research Site
Woolloongabba, 4102
Belgium4 sites
Research Site
Belgium, 1200
Research Site
Bruges, 8000
Research Site
Ghent, 9000
Research Site
Leuven, 3000
Canada4 sites
Research Site
Edmonton, Alberta, t6G1Z2
Research Site
Ste-Foy, Quebec, G1V 4G2
Research Site
Toronto, Ontario, M4N 3M5
Research Site
Toronto, Ontario, M5G 2M9
South Korea4 sites
Research Site
Goyang, 410-769
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
United Kingdom4 sites
Research Site
Cambridge, CB2 0QQ
Research Site
Chelsea, SW3 6JJ
Research Site
Manchester, M20 4BX
Research Site
Northwood, HA6 2RN
About this study
Official title: A Randomised, Open-Label, Phase 2 Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Unresectable or Advanced Melanoma and Primary or Secondary Resistance to PD-(L)1 Inhibition
Main study: This is an open-label, phase 2 study that aims to evaluate the efficacy and safety/tolerability of ceralasertib, when administered as monotherapy and in combination with durvalumab in participants with unresectable or advanced melanoma and primary or secondary resistance to PD-(L)1 inhibition.
Read the detailed description
Biopsy sub-study: This is an open-label, non-randomised, sub-study planned in participants suitable for 3 mandatory biopsies. Serial tumour biopsies are mandated in participants recruited into the sub-study and will be taken at baseline during the screening period, during treatment with ceralasertib monotherapy and during the off-treatment period of ceralasertib monotherapy.
- Conditions
- Melanoma
- Being tested
- Ceralasertib, Durvalumab
- Keywords
- Unresectable or Advanced Melanoma, Efficacy, Safety
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CeralasertibDrug
Ceralasertib (240 mg) will be administered orally twice daily.
DurvalumabBiological
Durvalumab (1500 mg) will be administered intravenously once every 28 days for participants who weight above > 30 kgs. For participants who weigh below ≤ 30 kgs, weight-based dosing equivalent to 20 mg/kg of durvalumab will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Main study: Ceralasertib + Durvalumab | Experimental | Participants 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. Receives: Drug: Ceralasertib; Biological: Durvalumab |
| Main study: Ceralasertib | Experimental | Participants 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. Receives: Drug: Ceralasertib |
| Biopsy Sub-study: Ceralasertib + Durvalumab | Experimental | From 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. Receives: Drug: Ceralasertib; Biological: Durvalumab |
| Biopsy study: Ceralasertib | Experimental | During Cycle 0, participants will receive ceralasertib on Days 1 to 7, followed by an off-treatment period between Days 8 to 28. Receives: Drug: Ceralasertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Main Study: Objective Response Rate (ORR)
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.
Measured: 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)
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-area in the Center Tumor Region
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.
Measured: Baseline, On-treatment (Cycle 0 Day 7), and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-area in the Invasive Margin Region
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.
Measured: Baseline, Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Center Tumor Region
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.
Measured: Baseline, On-treatment (Cycle 0 Day 7), and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Invasive Margin Region
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.
Measured: Baseline, and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Secondary outcomes (13)
Main Study and Biopsy Study: Duration of Response (DOR)
DOR was defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 or death due to any cause.
For main study BICR data is presented, and for Biopsy sub study, investigator assessment data has been presented.
Measured: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first
Main Study and Biopsy Study: Time to Response
Time to response was defined as the time from randomization until the date of first documented objective response, which is subsequently confirmed per RECIST 1.1.
For main study blinded independent central review (BICR) data is presented, and for Biopsy sub study, investigator assessment data has been presented.
Measured: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first
Main Study and Biopsy Study: Percentage Change From Baseline in Tumour Size
Percentage change from baseline in target lesion (TL) tumour size was assessed. Tumour size is the sum of the longest diameters of the target lesions. The percentage change from baseline in TL tumour size at post-baseline assessment is obtained for each participants taking the difference between the sum of the TLs at post baseline assessment and the sum of the TLs at baseline divided by the sum of the TLs at baseline times 100. Percentage change from baseline at 16 weeks for main study and 20 weeks for biopsy study in sum of target lesions has been presented.
For main study, BICR data is presented, and for Biopsy sub study, investigator assessment data has been presented.
Measured: Main Study: at 16 weeks; Biopsy study: at 20 weeks
Main Study and Biopsy Study: Progression Free Survival (PFS)
PFS was defined as time from randomization until progression per RECIST 1.1 or death due to any cause.
For main study BICR data is presented, and for Biopsy sub study, investigator assessment data has been presented.
Measured: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first
Main Study and Biopsy Study: Overall Survival (OS)
OS was defined as time from date of randomization until the date of death due to any cause.
Measured: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first
Main Study: Plasma Concentration of Ceralasertib
Pharmacokinetic (PK) of ceralasertib alone and when in combination with durvalumab was assessed.
Measured: From Cycle 1 to Cycle 4: Day 7 and Day 8 of each cycle (each cycle is 28 days); 90 days follow-up
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs)
The safety and tolerability of ceralasertib monotherapy and ceralasertib plus durvalumab in participants with unresectable or advanced melanoma and primary or secondary resistance to a programmed death ligand 1 (PD-[L] 1) inhibitor was assessed.
The grading scales found in the revised National Cancer Institute CTCAE latest version was utilized for all events with an assigned CTCAE grading. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 where Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening, urgent intervention required; Grade 5: Death related to AE.
Measured: From screening (Day -28 to -1) until Safety follow-up (30 days after last dose of Ceralasertib monotherapy or 90 days after last dose of Ceralasertib+Durvalumab combination) or data cut-off (2 years), whichever occurred first
Biopsy Study: Number of Participants With Presence of PD-L1 Overtime
Pre-treatment presence and/or on-treatment and/or off-treatment changes in PD-L1 was assessed to collect tumour tissue samples, or utilise residual samples, for the analysis of tumoural biomarkers that change following treatment with ceralasertib was assessed.
As per planned in protocol, this outcome measure was assessed only for biopsy study. The number of patients with PD-L1 expression <1% and >= 1% has been presented.
Measured: Baseline, On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Number of Participants With Presence of pRAD50
Pre-treatment presence and/or on-treatment and/or off-treatment changes in pRAD50 was assessed to collect tumour tissue samples, or utilise residual samples, for the analysis of tumoural biomarkers that change following treatment with ceralasertib was assessed.
As per planned in protocol, this outcome measure was assessed only for biopsy study.
Measured: On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Change From Baseline in Proliferation (Using Ki67+ Marker) of Carcinoma and/or Immune Cells (Including CD8+ T Cells) - Cell Density in Center Tumour Region
Changes in the proliferation of carcinoma and/or immune cells within tumours induced by ceralasertib monotherapy was assessed.
As per planned in protocol, this outcome measure was assessed only for biopsy study.
Measured: Baseline, On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Change From Baseline in Proliferation (Using Ki67+ Marker) of Carcinoma and/or Immune Cells (Including CD8+ T Cells) - Cell Density in Invasive Margin Region
Changes in the proliferation of carcinoma and/or immune cells within tumours induced by ceralasertib monotherapy was assessed.
As per planned in protocol, this outcome measure was assessed only for biopsy study.
Measured: Baseline, On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Change From Baseline in Proliferation (Using Ki67+ Marker) of Carcinoma and/or Immune Cells (Including CD8+ T Cells) - Area in Centre Tumour Region
Changes in the proliferation of carcinoma and/or immune cells within tumours induced by ceralasertib monotherapy was assessed.
As per planned in protocol, this outcome measure was assessed only for biopsy study.
Measured: Baseline, On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Change From Baseline in Proliferation (Using Ki67+ Marker) of Carcinoma and/or Immune Cells (Including CD8+ T Cells) - Area in Invasive Margin Region
Changes in the proliferation of carcinoma and/or immune cells within tumours induced by ceralasertib monotherapy was assessed.
As per planned in protocol, this outcome measure was assessed only for biopsy study.
Measured: Baseline, On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2021
- Study start11 Aug 2022
- Primary completion12 Apr 2024
- Study completion2 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 194 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05061134
- Sponsor's protocol ID
- D533AC00001
- Other IDs
- 2024-512378-91-00, 2021-001722-21
- Acronym
- MONETTE
- Status last verified
- Jul 2025
- First submitted
- 22 Sep 2021
- Last updated
- 31 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Open-Label, Phase 2 Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Unresectable or Advanced Melanoma and Primary or Secondary Resistance to PD-(L)1 Inhibition
- ClinicalTrials.gov ID
- NCT05061134
- Acronym / sponsor ID
- MONETTE / D533AC00001
- Conditions
- Melanoma
- Keywords
- Unresectable or Advanced Melanoma, Efficacy, Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 194 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 11 Aug 2022 (actual)
- Primary completion
- 12 Apr 2024 (actual)
- Study completion
- 2 Nov 2026 (estimated)
- First posted
- 29 Sep 2021 (actual)
- Results
- Posted 21 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Main study: This is an open-label, phase 2 study that aims to evaluate the efficacy and safety/tolerability of ceralasertib, when administered as monotherapy and in combination with durvalumab in participants with unresectable or advanced melanoma and primary or secondary resistance to PD-(L)1 inhibition.
Detailed description
Biopsy sub-study: This is an open-label, non-randomised, sub-study planned in participants suitable for 3 mandatory biopsies. Serial tumour biopsies are mandated in participants recruited into the sub-study and will be taken at baseline during the screening period, during treatment with ceralasertib monotherapy and during the off-treatment period of ceralasertib monotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Main study: Ceralasertib + Durvalumab | Experimental | Drug: Ceralasertib, Biological: DurvalumabParticipants 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: Ceralasertib | Experimental | Drug: CeralasertibParticipants 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 + Durvalumab | Experimental | Drug: Ceralasertib, Biological: DurvalumabFrom 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: Ceralasertib | Experimental | Drug: CeralasertibDuring Cycle 0, participants will receive ceralasertib on Days 1 to 7, followed by an off-treatment period between Days 8 to 28. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Participants must have a histologically or cytologically confirmed diagnosis of unresectable or metastatic melanoma of cutaneous, acral or mucosal subtype
- Availability of an archival tumour sample and a fresh tumour biopsy taken at screening
- Patient must have received at least 1 prior immunotherapy (anti-PD-(L)1 ± anti-CTLA-4 [Cytotoxic T-lymphocyte-associated protein 4]) for a minimum of 6 weeks and no more than 2 prior regimens in the metastatic setting. Patients must have confirmed progression during treatment with a PD-(L)1 inhibitor +/- a CTLA-4 inhibitor.
- The interval between the last dose of anti-PD-(L)1, BRAF/MEK (B-Rapidly Accelerated Fibrosarcoma gene/mitogen-activated protein kinase gene) inhibitor and the first dose of the study regimen must be a minimum of 14 days
- Measurable disease by RECIST 1.1.
Key exclusion criteria (9 listed)
- Patients must not have experienced a toxicity that led to permanent discontinuation of prior checkpoint inhibitors (CPI) treatment.
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 3 years before the first dose of study treatment
- Uveal melanoma
- Must not have experienced a Grade ≥ 3 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy
- History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the study clinical lead.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CeralasertibCeralasertib (240 mg) will be administered orally twice daily. | Drug | Biopsy Sub-study: Ceralasertib + Durvalumab, Biopsy study: Ceralasertib, Main study: Ceralasertib, Main study: Ceralasertib + Durvalumab |
| DurvalumabDurvalumab (1500 mg) will be administered intravenously once every 28 days for participants who weight above > 30 kgs. For participants who weigh below ≤ 30 kgs, weight-based dosing equivalent to 20 mg/kg of durvalumab will be administered. | Biological | Biopsy Sub-study: Ceralasertib + Durvalumab, Main study: Ceralasertib + Durvalumab |
Primary outcome
Main Study: Objective Response Rate (ORR)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
13 secondary outcomes
Main Study and Biopsy Study: Duration of Response (DOR)
Time frame: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first
Main Study and Biopsy Study: Time to Response
Time frame: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first
Main Study and Biopsy Study: Percentage Change From Baseline in Tumour Size
Time frame: Main Study: at 16 weeks; Biopsy study: at 20 weeks
Main Study and Biopsy Study: Progression Free Survival (PFS)
Time frame: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first
Main Study and Biopsy Study: Overall Survival (OS)
Time frame: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first
Main Study: Plasma Concentration of Ceralasertib
Time frame: From Cycle 1 to Cycle 4: Day 7 and Day 8 of each cycle (each cycle is 28 days); 90 days follow-up
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs)
Time frame: From screening (Day -28 to -1) until Safety follow-up (30 days after last dose of Ceralasertib monotherapy or 90 days after last dose of Ceralasertib+Durvalumab combination) or data cut-off (2 years), whichever occurred first
Biopsy Study: Number of Participants With Presence of PD-L1 Overtime
Time frame: Baseline, On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Number of Participants With Presence of pRAD50
Time frame: On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Change From Baseline in Proliferation (Using Ki67+ Marker) of Carcinoma and/or Immune Cells (Including CD8+ T Cells) - Cell Density in Center Tumour Region
Time frame: Baseline, On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Change From Baseline in Proliferation (Using Ki67+ Marker) of Carcinoma and/or Immune Cells (Including CD8+ T Cells) - Cell Density in Invasive Margin Region
Time frame: Baseline, On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Change From Baseline in Proliferation (Using Ki67+ Marker) of Carcinoma and/or Immune Cells (Including CD8+ T Cells) - Area in Centre Tumour Region
Time frame: Baseline, On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Biopsy Study: Change From Baseline in Proliferation (Using Ki67+ Marker) of Carcinoma and/or Immune Cells (Including CD8+ T Cells) - Area in Invasive Margin Region
Time frame: Baseline, On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- D533AC00001\_CSP\_RedactedLink provided by the sponsor.
- D533AC00001\_SAP\_RedactedLink provided by the sponsor.
- D533AC00001\_CSR synopsis\_RedactedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
66 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ceralasertib and Durvalumab in people with Melanoma, run by AstraZeneca at 66 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 66 sites in Germany, France, Spain, Italy, United States and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Main Study: Objective Response Rate (ORR) (time frame: 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)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2025.