A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer

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

Time frame: 2 years 4 months

Population: Evaluable for response set included all participants who were Molecularly Eligible Centrally Confirmed evaluable for response set with measurable disease at baseline and who received at least 1 dose of study intervention.

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

Time frame: Up to 2 years 4 months

Population: Evaluable for response set included all participants who were Molecularly Eligible Centrally Confirmed evaluable for response set with measurable disease at baseline or unfavorable CTC count and who received at least 1 dose of study intervention.

The adverse events as a variable of safety and tolerability after admiration of ceralasertib was determined.

Time frame: From Screening (Day -28 to Day -1) Until Follow-up (30 days post last dose), up to 2 years 4 months

Population: The safety analysis consists of all the participants who received at least 1 dose of ceralasterib.

DoR is defined as the time from the date of first documented response (confirmed CR/PR) until date of documented progression or death in the absence of disease progression.

Time frame: Up to 2 years 4 months

Population: Molecularly eligible centrally confirmed evaluable for response set included all participants who were Molecularly Eligible Centrally Confirmed with measurable baseline disease and who received at least 1 dose of study intervention. The number of responders who subsequently progressed or died was 0, therefore, efficacy analysis was not conducted for Duration of response (DoR).

Percentage change in tumour size is defined as the reduction from baseline or the increase from baseline in the absence of a reduction in the sum of the longest diameters (or the short axis measurements for lymph nodes) of the target lesions. A negative change denotes a reduction in target lesion size.

Time frame: Scan Visits 1 (Week 8), 2 (Week 16), 3 (Week 24), 4 (Week 32), 5 (Week 40), 6 (Week (48), 7 (Week 56)

Population: Molecularly eligible centrally confirmed evaluable for response set included all participants who were Molecularly Eligible Centrally Confirmed with measurable baseline disease and who received at least 1 dose of study intervention. Percentage change in tumor size was conducted every 8 weeks after the start of the treatment up to 1 year, then every 12 weeks until objective disease progression as per RECIST 1.1 or PCWG3 criteria.

PFS is defined as the time from start of study intervention until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy prior to progression. Progression is defined using (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.

Time frame: Up to 2 years 4 months

Population: Molecularly eligible centrally confirmed set included all participants who were Molecularly Eligible Centrally Confirmed and who received at least 1 dose of study intervention.

Percentage change in tumour size is defined as the reduction from baseline or the increase from baseline in the absence of a reduction in the sum of the longest diameters (or the short axis measurements for lymph nodes) of the target lesions. A negative change denotes a reduction in target lesion size. Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.

Time frame: Scan Visits 1 (Week 8), 2 (Week 16), 3 (Week 24), 4 (Week 32)

Population: Molecularly eligible centrally confirmed evaluable for response set included all participants who were Molecularly Eligible Centrally Confirmed with measurable baseline disease and who received at least 1 dose of study intervention. Percentage change in tumor size was conducted every 8 weeks after the start of the treatment up to 1 year, then every 12 weeks until objective disease progression as per RECIST 1.1 or PCWG3 criteria.