A Study of Ceralasertib Monotherapy and Ceralasertib Plus... | NCT05061134

ID	Type	Description	Link
2024-512378-91-00	Registry Identifier	CTIS
2021-001722-21	EudraCT Number

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	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.	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.	Drug: Ceralasertib

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Ceralasertib	Drug	Ceralasertib (240 mg) will be administered orally twice daily.	Biopsy Sub-study: Ceralasertib + Durvalumab Biopsy study: Ceralasertib

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	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.	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.	Baseline, On-treatment (Cycle 0 Day 7), and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

Secondary Outcomes

Measure	Description	Time Frame
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.	Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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
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.

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Los Angeles	California	90024	United States
Research Site

Label	URL
D533AC00001\_CSP\_Redacted	View source
D533AC00001\_SAP\_Redacted	View source

IPD Sharing Statement Module

ID	Title	Description
FG000	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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 17, 2024	Mar 24, 2025

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

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.

Posted

Number

95% Confidence Interval

Percentage of participants

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)

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00097 OG00152

Title

Denominators

Categories

Title	Measurements
	OG0009.3(4.3 to 16.9) OG0015.8(1.2 to 15.9)

Primary

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.

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.

Posted

Mean

Standard Deviation

Percent change

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Secondary

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.

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.

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

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.

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

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.

Posted

Mean

Standard Deviation

Percentage change from baseline

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

ID	Title	Description
OG000	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.
OG001

Secondary

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.

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.

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

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.

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.

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Main Study: Plasma Concentration of Ceralasertib

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

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanograms per milliliter (ng/mL)

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

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.

Safety analysis set included all participants who received at least 1 dose of study treatment. Participants were summarized according to the actual treatment received.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000

Secondary

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.

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Secondary

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.

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Secondary

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.

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.

Posted

Mean

Standard Deviation

Change in cells per mm2

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Primary

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.

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.

Posted

Median

Full Range

Percent change

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Primary

Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Center Tumor Region

Posted

Mean

Standard Deviation

Change in cells per mm^2

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Primary

Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Invasive Margin Region

Posted

Median

Full Range

Change in cells per mm^2

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Secondary

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.

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.

Posted

Median

Full Range

Change in cells per mm2

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Secondary

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.

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.

Posted

Mean

Standard Deviation

Percent change

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Secondary

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.

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.

Posted

Median

Full Range

Percent change

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	43	100	19	97	86	97
EG001	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.	23	51	5	52	43	52
EG002	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.	14	41	9	41	34	41

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cellulitis	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Device related infection	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Pneumonia	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0002 events2 affected97 at risk EG0010 events0 affected52 at risk EG0022 events2 affected41 at risk
Pneumonia aspiration	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Proteus infection	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Sepsis	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0021 events1 affected41 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0021 events1 affected41 at risk
Urosepsis	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected52 at risk EG0021 events1 affected41 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Non-systematic Assessment	EG0005 events3 affected97 at risk EG0011 events1 affected52 at risk EG0020 events0 affected41 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Cerebral infarction	Nervous system disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Seizure	Nervous system disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected52 at risk EG0020 events0 affected41 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Non-systematic Assessment	EG0002 events2 affected97 at risk EG0010 events0 affected52 at risk EG0021 events1 affected41 at risk
Gastritis	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected52 at risk EG0020 events0 affected41 at risk
Haemoperitoneum	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected52 at risk EG0020 events0 affected41 at risk
Immune-mediated enterocolitis	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG0002 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG0003 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Chills	General disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Non-cardiac chest pain	General disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Pyrexia	General disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Troponin increased	Investigations	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Arthritis bacterial	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0021 events1 affected41 at risk
COVID-19	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0021 events1 affected41 at risk
Gastroenteritis	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0021 events1 affected41 at risk
Gastroenteritis norovirus	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0021 events1 affected41 at risk
Syncope	Nervous system disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0021 events1 affected41 at risk
Colitis	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0021 events1 affected41 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0021 events1 affected41 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0021 events1 affected41 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG0003 events3 affected97 at risk EG0014 events3 affected52 at risk EG0020 events0 affected41 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.0	Non-systematic Assessment	EG00012 events7 affected97 at risk EG0012 events2 affected52 at risk EG0020 events0 affected41 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Non-systematic Assessment	EG00055 events35 affected97 at risk EG00112 events9 affected52 at risk EG00220 events15 affected41 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 27.0	Non-systematic Assessment	EG0008 events5 affected97 at risk EG0012 events1 affected52 at risk EG0020 events0 affected41 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Non-systematic Assessment	EG00017 events7 affected97 at risk EG0013 events2 affected52 at risk EG00212 events4 affected41 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 27.0	Non-systematic Assessment	EG00014 events6 affected97 at risk EG0016 events3 affected52 at risk EG00213 events5 affected41 at risk
Hypothyroidism	Endocrine disorders	MedDRA 27.0	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0016 events3 affected52 at risk EG0020 events0 affected41 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.0	Non-systematic Assessment	EG00030 events20 affected97 at risk EG00114 events12 affected52 at risk EG00214 events11 affected41 at risk
Headache	Nervous system disorders	MedDRA 27.0	Non-systematic Assessment	EG00029 events13 affected97 at risk EG0015 events3 affected52 at risk EG0027 events6 affected41 at risk
Hypertension	Vascular disorders	MedDRA 27.0	Non-systematic Assessment	EG0005 events4 affected97 at risk EG0016 events4 affected52 at risk EG0020 events0 affected41 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Non-systematic Assessment	EG0008 events7 affected97 at risk EG00110 events8 affected52 at risk EG0025 events5 affected41 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Non-systematic Assessment	EG0003 events3 affected97 at risk EG0014 events4 affected52 at risk EG0027 events7 affected41 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG00014 events10 affected97 at risk EG0012 events1 affected52 at risk EG0026 events6 affected41 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG00011 events10 affected97 at risk EG0011 events1 affected52 at risk EG00210 events8 affected41 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG00019 events11 affected97 at risk EG0018 events6 affected52 at risk EG00215 events11 affected41 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG0005 events5 affected97 at risk EG0011 events1 affected52 at risk EG0026 events3 affected41 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG000100 events50 affected97 at risk EG00125 events19 affected52 at risk EG00238 events20 affected41 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG00033 events21 affected97 at risk EG0019 events8 affected52 at risk EG00221 events13 affected41 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.0	Non-systematic Assessment	EG00023 events17 affected97 at risk EG0017 events5 affected52 at risk EG0020 events0 affected41 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Non-systematic Assessment	EG00012 events9 affected97 at risk EG0014 events4 affected52 at risk EG0020 events0 affected41 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Non-systematic Assessment	EG0008 events5 affected97 at risk EG0013 events3 affected52 at risk EG0020 events0 affected41 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Non-systematic Assessment	EG00015 events11 affected97 at risk EG0016 events5 affected52 at risk EG0020 events0 affected41 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Non-systematic Assessment	EG0009 events8 affected97 at risk EG0012 events2 affected52 at risk EG00211 events4 affected41 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Non-systematic Assessment	EG0007 events6 affected97 at risk EG0012 events2 affected52 at risk EG0024 events3 affected41 at risk
Asthenia	General disorders	MedDRA 27.0	Non-systematic Assessment	EG00033 events22 affected97 at risk EG00113 events11 affected52 at risk EG00212 events8 affected41 at risk
Chills	General disorders	MedDRA 27.0	Non-systematic Assessment	EG0008 events5 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Fatigue	General disorders	MedDRA 27.0	Non-systematic Assessment	EG00022 events19 affected97 at risk EG00117 events14 affected52 at risk EG00214 events10 affected41 at risk
Influenza like illness	General disorders	MedDRA 27.0	Non-systematic Assessment	EG0006 events5 affected97 at risk EG0010 events0 affected52 at risk EG0020 events0 affected41 at risk
Pyrexia	General disorders	MedDRA 27.0	Non-systematic Assessment	EG00014 events11 affected97 at risk EG0013 events3 affected52 at risk EG0024 events3 affected41 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Non-systematic Assessment	EG0008 events7 affected97 at risk EG0014 events4 affected52 at risk EG0026 events5 affected41 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Non-systematic Assessment	EG0009 events8 affected97 at risk EG0013 events3 affected52 at risk EG0025 events4 affected41 at risk
C-reactive protein increased	Investigations	MedDRA 27.0	Non-systematic Assessment	EG0008 events5 affected97 at risk EG0012 events2 affected52 at risk EG0020 events0 affected41 at risk
Lipase increased	Investigations	MedDRA 27.0	Non-systematic Assessment	EG00011 events10 affected97 at risk EG0013 events3 affected52 at risk EG0028 events7 affected41 at risk
Neutrophil count decreased	Investigations	MedDRA 27.0	Non-systematic Assessment	EG0002 events2 affected97 at risk EG0016 events4 affected52 at risk EG0020 events0 affected41 at risk
Platelet count decreased	Investigations	MedDRA 27.0	Non-systematic Assessment	EG00014 events10 affected97 at risk EG0014 events3 affected52 at risk EG0020 events0 affected41 at risk
Amylase increased	Investigations	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0024 events3 affected41 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0024 events3 affected41 at risk
Dizziness	Nervous system disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0023 events3 affected41 at risk
Paraesthesia	Nervous system disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0024 events3 affected41 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0024 events3 affected41 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0023 events3 affected41 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0025 events4 affected41 at risk
Insomnia	Psychiatric disorders	MedDRA 27.0	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected52 at risk EG0023 events3 affected41 at risk

ID	Term
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009380	Neoplasms, Nerve Tissue
D018326	Nevi and Melanomas
D012878	Skin Neoplasms
D009371	Neoplasms by Site
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups