Trial Outcomes & Findings for A Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Melanoma and Resistance to PD-(L)1 Inhibition (NCT NCT05061134)

Last Updated: 2025-07-31

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

194 participants

Primary outcome timeframe

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)

Results posted on

2025-07-31

Participant Flow

This study was conducted between 11 Aug 2022 (first participants enrolled) to 12 Apr 2024 (primary completion date). The study was conducted in 11 countries.

Participants who met the inclusion criteria and none of the exclusion criteria were enrolled to the study. Informed consent forms (ICFs) was signed prior to screening procedures. All study assessments were performed as per the Schedule of Activities.

Participant milestones

Participant milestones
Measure	Main Study: Ceralasertib + Durvalumab Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Overall Study STARTED	100	51	43
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	100	51	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Main Study: Ceralasertib + Durvalumab Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Overall Study Patients ongoing in the study at data cut-off (DCO) of 12-April-2024	19	3	6
Overall Study Subject not treated	0	0	2
Overall Study Other	0	0	9
Overall Study Withdrawal by Subject	9	8	5
Overall Study Study Terminated by Sponsor	22	14	7
Overall Study Progressive Disease	1	2	0
Overall Study Patient Is on Survival Follow Up Beyond DCO	1	0	0
Overall Study Lost to Follow-up	1	0	0
Overall Study Physician Decision	1	1	0
Overall Study Disease progression	1	0	0
Overall Study Death	43	23	14
Overall Study Database lock	2	0	0

Baseline Characteristics

A Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Melanoma and Resistance to PD-(L)1 Inhibition

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Main Study: Ceralasertib + Durvalumab n=100 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy n=51 Participants Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab n=41 Participants Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Total n=192 Participants Total of all reporting groups
Age, Continuous	62.9 Years STANDARD_DEVIATION 13.6 • n=5 Participants	62.9 Years STANDARD_DEVIATION 12.6 • n=7 Participants	61.4 Years STANDARD_DEVIATION 11.9 • n=5 Participants	62.6 Years STANDARD_DEVIATION 13.0 • n=4 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	22 Participants n=7 Participants	16 Participants n=5 Participants	80 Participants n=4 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	29 Participants n=7 Participants	25 Participants n=5 Participants	112 Participants n=4 Participants
Race/Ethnicity, Customized White	79 Participants n=5 Participants	39 Participants n=7 Participants	31 Participants n=5 Participants	149 Participants n=4 Participants
Race/Ethnicity, Customized Asian	9 Participants n=5 Participants	7 Participants n=7 Participants	0 Participants n=5 Participants	16 Participants n=4 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Not reported	10 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants	24 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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)

Population: Safety analysis set included all participants who received at least 1 dose of study treatment. Participants were summarized according to the actual treatment received. Here, two participants, who were randomized to the Main Study: Ceralasertib + Durvalumab group, started with ceralasertib but did not receive durvalumab. Hence, they are summarized in the Main Study: Ceralasertib monotherapy group (actual treatment group) for the outputs presented in the safety analysis set.

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=97 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy n=52 Participants Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Main Study: Objective Response Rate (ORR)	9.3 Percentage of participants Interval 4.3 to 16.9	5.8 Percentage of participants Interval 1.2 to 15.9	—

PRIMARY outcome

Timeframe: Baseline, On-treatment (Cycle 0 Day 7), and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

Population: Pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of study treatment with at least 1 reportable post-baseline pharmacodynamic measurement. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=23 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-area in the Center Tumor Region On-treatment	-0.976 Percent change Standard Deviation 2.920	—	—
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-area in the Center Tumor Region Off-treatment	-0.451 Percent change Standard Deviation 1.357	—	—

PRIMARY outcome

Timeframe: Baseline, Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

Population: The PD analysis set included all participants who received at least 1 dose of study treatment with at least 1 reportable post-baseline pharmacodynamic measurement. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=1 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-area in the Invasive Margin Region	NA Percent change Interval -0.73 to -0.73 As pre-specified in statistical analysis plan (SAP), median is not calculable due to insufficient number of participants.	—	—

PRIMARY outcome

Timeframe: Baseline, On-treatment (Cycle 0 Day 7), and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=23 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Center Tumor Region On-treatment	-183.589 Change in cells per mm^2 Standard Deviation 740.398	—	—
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Center Tumor Region Off-treatment	-85.259 Change in cells per mm^2 Standard Deviation 396.091	—	—

PRIMARY outcome

Timeframe: Baseline, and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=1 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Invasive Margin Region	NA Change in cells per mm^2 Interval -235.53 to -235.53 As pre-specified in statistical analysis plan (SAP), median is not calculable due to insufficient number of participants.	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first

Population: Safety analysis set included all participants who received at least 1 dose of study treatment. Participants were summarized according to the actual treatment received. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure and participants with objective response.

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.

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=9 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy n=3 Participants Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab n=2 Participants Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Main Study and Biopsy Study: Duration of Response (DOR)	NA Months Interval 7.5 to Here, NA indicate that median and upper limit of 95% CI were not evaluable due to insufficient number of participants with events.	NA Months Interval 5.6 to Here, NA indicate that median and upper limit of 95% CI were not evaluable due to insufficient number of participants with events.	NA Months Interval 5.8 to Here, NA indicate that median and upper limit of 95% CI were not evaluable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first

Population: Safety analysis set included all participants who received at least 1 dose of study treatment. Participants were summarized according to the actual treatment received. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure and participants with objective 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.

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=9 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy n=3 Participants Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab n=2 Participants Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Main Study and Biopsy Study: Time to Response	3.5 Months Interval 1.7 to 5.6	3.6 Months Interval 2.4 to Here, NA indicate that upper limit of 95% CI was not evaluable due to insufficient number of participants with events.	3.7 Months Interval 2.7 to Here, NA indicate that upper limit of 95% CI was not evaluable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Main Study: at 16 weeks; Biopsy study: at 20 weeks

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.

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=76 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy n=41 Participants Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab n=29 Participants Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Main Study and Biopsy Study: Percentage Change From Baseline in Tumour Size	15.80 Percentage change from baseline Standard Deviation 38.14	11.25 Percentage change from baseline Standard Deviation 33.99	17.93 Percentage change from baseline Standard Deviation 38.46

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first

Population: For main study: Full analysis set included all participants who were randomized in the study. For biopsy study: Safety analysis set included all participants who received at least 1 dose of study treatment. Participants were summarized according to the actual treatment received.

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.

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=100 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy n=51 Participants Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab n=41 Participants Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Main Study and Biopsy Study: Progression Free Survival (PFS)	2.00 Months Interval 1.91 to 3.52	1.94 Months Interval 1.91 to 3.06	2.83 Months Interval 2.76 to 4.47

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first

OS was defined as time from date of randomization until the date of death due to any cause.

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=100 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy n=51 Participants Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab n=41 Participants Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Main Study and Biopsy Study: Overall Survival (OS)	16.00 Months Interval 10.48 to Here, NA indicate that upper limit of 95% CI was not evaluable due to insufficient number of participants with events and due to the duration of follow-up.	12.32 Months Interval 9.46 to Here, NA indicate that upper limit of 95% CI was not evaluable due to insufficient number of participants with events and due to the duration of follow-up.	NA Months Interval 10.18 to Here, NA indicate that median and upper limit of 95% CI was not evaluable due to insufficient number of participants with events and due to the duration of follow-up.

SECONDARY outcome

Timeframe: From Cycle 1 to Cycle 4: Day 7 and Day 8 of each cycle (each cycle is 28 days); 90 days follow-up

Population: The PK analysis set included all dosed participants with reportable ceralasertib or durvalumab plasma concentrations. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure and 'number analyzed in each row' signifies the participants with available data that were analyzed for specified timepoint.

Pharmacokinetic (PK) of ceralasertib alone and when in combination with durvalumab was assessed.

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=85 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy n=41 Participants Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Main Study: Plasma Concentration of Ceralasertib Cycle 2 Day 8: 1 hour post-dose	425900 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 36.73	—	—
Main Study: Plasma Concentration of Ceralasertib Cycle 3 Day 7: pre-dose	4269 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 44.72	4045 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 51.17	—
Main Study: Plasma Concentration of Ceralasertib Cycle 1 Day 7: pre-dose	4621 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 68.34	4789 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 52.03	—
Main Study: Plasma Concentration of Ceralasertib Cycle 1 Day 7: 1 hour post-dose	8304 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 44.69	8010 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 53.84	—
Main Study: Plasma Concentration of Ceralasertib Cycle 1 Day 8: pre-dose	78.10 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 43.66	—	—
Main Study: Plasma Concentration of Ceralasertib Cycle 1 Day 8: 1 hour post-dose	379600 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 23.05	—	—
Main Study: Plasma Concentration of Ceralasertib Cycle 2 Day 7: pre-dose	4487 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 70.46	4101 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 40.53	—
Main Study: Plasma Concentration of Ceralasertib Cycle 2 Day 7: 1 hour post-dose	7735 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 53.09	7984 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 45.39	—
Main Study: Plasma Concentration of Ceralasertib Cycle 2 Day 8: pre-dose	67170 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 47.38	—	—
Main Study: Plasma Concentration of Ceralasertib Cycle 3 Day 7: 1 hour post-dose	7072 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 41.81	7799 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 41.76	—
Main Study: Plasma Concentration of Ceralasertib Cycle 3 Day 8: pre-dose	105100 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 50.26	—	—
Main Study: Plasma Concentration of Ceralasertib Cycle 3 Day 8: 1 hour post-dose	460800 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 26.48	—	—
Main Study: Plasma Concentration of Ceralasertib Cycle 4 Day 7: pre-dose	—	NA Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA Here, geometric mean and geometric Coefficient of Variation could not be calculated due to insufficient number of participants as pre-specified in the SAP.	—
Main Study: Plasma Concentration of Ceralasertib Cycle 4 Day 7: 1 hour post-dose	—	7273 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 33.82	—
Main Study: Plasma Concentration of Ceralasertib 90 Days Follow-up	23830 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 79.06	—	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Main Study: Ceralasertib + Durvalumab n=97 Participants Participants received ceralasertib 240 milligrams (mg) orally twice daily (BD) for 7 consecutive days (Days 1 to 7), and on Day 8, participants received 1500 mg durvalumab as an intravenous (IV) infusion once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Main Study: Ceralasertib Monotherapy n=52 Participants Participants received ceralasertib monotherapy 240 mg orally BD from Days 1 to 7, once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.	Biopsy Study: Ceralasertib + Durvalumab n=41 Participants Participants received ceralasertib monotherapy 240 mg orally BD for 7 consecutive days (Days 1 to 7) on Cycle 0. Onwards Cycle 1, participants received ceralasertib 240 mg orally BD for 7 consecutive days (Days 1 to 7) plus durvalumab 1500 mg as IV infusion on Day 8 once in every 28 days. This 28-day cycle was repeated until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion was met.
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE	92 Participants	45 Participants	39 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE possibly related to treatment	74 Participants	36 Participants	29 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE of >= CTCAE grade 3	34 Participants	16 Participants	13 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE of >= CTCAE grade 3, possibly related to treatment	17 Participants	9 Participants	4 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE	19 Participants	5 Participants	9 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE possibly related to treatment	3 Participants	2 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE of >= CTCAE grade 3	16 Participants	3 Participants	9 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE of >= CTCAE grade 3, possibly related to treatment	3 Participants	0 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE with outcome death	0 Participants	0 Participants	1 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE with outcome death, possibly related to treatment	0 Participants	0 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to discontinuation of treatment	1 Participants	1 Participants	1 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to discontinuation of treatment, possibly related to treatment	1 Participants	1 Participants	1 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to drug interruption of treatment	8 Participants	3 Participants	8 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to dose reduction of treatment	10 Participants	6 Participants	3 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to dose modification of treatment	14 Participants	8 Participants	9 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to discontinuation of treatment	0 Participants	0 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to discontinuation of treatment, possibly related to treatment	0 Participants	0 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to drug interruption of treatment	5 Participants	1 Participants	4 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to dose reduction of treatment	2 Participants	0 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to dose modification of treatment	5 Participants	1 Participants	4 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE of >= CTCAE grade 3, possibly related to Ceralasertib	16 Participants	9 Participants	4 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE of >= CTCAE grade 3, possibly related to Durvalumab	5 Participants	—	1 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE possibly related to Ceralasertib	3 Participants	2 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE possibly related to Durvalumab	1 Participants	—	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE of >= CTCAE grade 3, possibly related to Ceralasertib	3 Participants	0 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE of >= CTCAE grade 3, possibly related to Durvalumab	1 Participants	—	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE with outcome death, possibly related to Ceralasertib	0 Participants	0 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE with outcome death, possibly related to Durvalumab	0 Participants	—	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to discontinuation of Ceralasertib	1 Participants	1 Participants	1 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to discontinuation of Durvalumab	0 Participants	—	1 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to discontinuation of Ceralasertib, possibly related to Ceralasertib	1 Participants	1 Participants	1 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to discontinuation of Durvalumab, possibly related to Durvalumab	0 Participants	—	1 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to drug interruption of Ceralasertib	6 Participants	3 Participants	8 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to drug interruption of Durvalumab	5 Participants	—	2 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to dose reduction of Ceralasertib	10 Participants	6 Participants	3 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to dose reduction of Durvalumab	0 Participants	—	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to dose modification of Ceralasertib	13 Participants	8 Participants	9 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any AE leading to dose modification of Durvalumab	5 Participants	—	2 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to discontinuation of Ceralasertib	0 Participants	0 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to discontinuation of Durvalumab	0 Participants	—	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to discontinuation of Ceralasertib, possibly related to Ceralasertib	0 Participants	0 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to discontinuation of Durvalumab, possibly related to Durvalumab	0 Participants	—	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to drug interruption of Ceralasertib	4 Participants	1 Participants	4 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to drug interruption of Durvalumab	3 Participants	—	1 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to dose reduction of Ceralasertib	2 Participants	0 Participants	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to dose reduction of Durvalumab	0 Participants	—	0 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to dose modification of Ceralasertib	4 Participants	1 Participants	4 Participants
Main Study and Biopsy Study: Number of Participants With Adverse Events (AEs) Any SAE leading to dose modification of Durvalumab	3 Participants	—	1 Participants

SECONDARY outcome

Timeframe: Baseline, On-treatment (Cycle 0 Day 7); Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)