Study of AZD2811 + Durvalumab in ES-SCLC

12 month landmark PFS, APF12, where PFS is defined as the time from the first dose of study intervention in the induction phase until objective disease progression (as assessed by the investigator per RECIST v1.1) or death from any cause, whichever comes first.

Time frame: Up to 12 months

Population: Evaluable population, defined as all participants who entered the maintenance phase and who received at least one dose/have been exposed to any AZD2811 + durvalumab. Only the AZD2811 + durvalumab arm could be evaluable.

Time frame: Up to Cycle 8 Day 8 (approximately 5 months)

Population: All subjects who received at least one dose of AZD2811 and/or durvalumab with at least one reportable concentration corresponding to the dosed study intervention (reportable means at least one concentration above lower limit of quantification (LLOQ))

The EORTC QLQ-LC13 is a 13-item questionnaire comprised of 1 symptom scale assessing dysponea, and a series of single questions assessing cough, haemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, and use of pain medication. All items are assessed using a Likert four-point scale (1= not at all to 4 = very much). An outcome variable consisting of a score from 0 to 100 is derived for the symptom scale and symptom items according to the EORTC QLQ-LC13 instructions (Fayers et al., 2001). The outcome variable is derived by taking the average of items contributing to a scale or the value of an individual item and applying a linear transformation to standardize the score, so that scores range from 0 to 100. Higher scores represent greater symptom severity.

Time frame: Up to Cycle 10 Day 1, approximately 7 months

Population: Evaluable population, defined as all participants who entered the maintenance phase and who received at least one dose/have been exposed to any AZD2811 + durvalumab. Only the AZD2811 + durvalumab arm could be evaluable.

The EORTC QLQ-LC13 is a 13-item questionnaire comprised of 1 symptom scale assessing dysponea, and a series of single questions assessing cough, haemoptysis, sore mouth, dysphagis, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, and use of pain medication. Use of pain medication is collected as a Yes/No response.

Time frame: Up to Cycle 10 Day 1, approximately 7 months

Population: Evaluable population, defined as all participants who entered the maintenance phase and who received at least one dose/have been exposed to any AZD2811 + durvalumab. Only the AZD2811 + durvalumab arm could be evaluable.

EORTC QLQ-C30 consists of 30 questions that can be combined to give 5 functional scales (physical, role, cognitive, emotional, social), 3 symptom scales (fatigue, pain, nausea/vomiting), 6 individual items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global measure of health status. QoL issues are assessed using a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) except 2 questions which are between 1 (Very Poor) and 7 (Excellent). An outcome variable consisting of a score from 0 to 100 is derived for each scale/item and global health status/QoL. The variable is derived by taking the average of items contributing to a scale or the value of an item and applying a linear transformation to standardize the score, so that scores range from 0 to 100. Higher scores on the global health status/QoL and functioning scales indicate better health status/function; higher scores on symptom scales/items represent worse symptoms.

Time frame: Up to Cycle 10 Day 1, approximately 7 months

Population: Evaluable population, defined as all participants who entered the maintenance phase and who received at least one dose/have been exposed to any AZD2811 + durvalumab. Only the AZD2811 + durvalumab arm could be evaluable.

6 and 9 month landmark PFS, APF6/APF9, where PFS is defined as the time from the first dose of study intervention in the induction phase until objective disease progression (as assessed by the investigator per RECIST v1.1) or death from any cause, whichever comes first.

Time frame: Up to 9 months

Population: Evaluable population, defined as all participants who entered the maintenance phase and who received at least one dose/have been exposed to any AZD2811 + durvalumab. The endpoint was not to be collected in patients who did not meet these criteria, so only the AZD2811 + durvalumab arm could be evaluable.

12, 15, and 18 month landmarks for Overall Survival (OS) which is defined as the time from the date of first dose of study intervention in the induction phase until death due to any cause, regardless of whether the participant withdraws from study therapy or received another anticancer therapy.

Time frame: Up to 18 months

Population: Evaluable population, defined as all participants who entered the maintenance phase and who received at least one dose/have been exposed to any AZD2811 + durvalumab. Only the AZD2811 + durvalumab arm could be evaluable.~The study was terminated early due to the emerging benefit/risk profile of AZD2811. Due to insufficient follow-up at the point of study termination, data were not collected for OS15 and OS18 so these endpoints could not be reported. Only OS12 could be reported.

Progression-free survival is defined as the time interval from the first dose of study intervention in the induction phase until the date of objective disease progression or death (by any cause, in the absence of progression) regardless of whether the participant withdraws from treatment or received another anticancer therapy prior to progression.

Time frame: Up to approximately 10 months

Population: Evaluable population, defined as all participants who entered the maintenance phase and who received at least one dose/have been exposed to any AZD2811 + durvalumab. Only the AZD2811+durvlumab arm could be evaluable.~Due to the early termination of study enrolment, data were not collected up to the intended time frame of 3 years.

Objective response rate is defined as the percentage of participants with confirmed objective response (CR or PR) per RECIST 1.1. A confirmed response of CR/PR means that a response of CR/PR is recorded at one visit and confirmed by repeat imaging not less than 4 weeks after the visit when the response was first observed with no evidence of progression between the initial and CR/PR confirmation visit.

Time frame: Up to approximately 10 months

Population: All dosed participants who had measurable disease at baseline. Note that participants were treated for 4 cycles on a Q3W schedule in the induction phase with platinum-based induction therapy (cisplatin or carboplatin plus etoposide) + durvalumab. Participants who had not progressed per RECIST v1.1 at the end of the induction phase and who met maintenance phase eligibility criteria continued into the maintenance phase of the trial and were treated with AZD2811 + durvalumab as maintenance therapy.

Overall survival is defined as the time from the date of first dose of study intervention in the induction phase until death due to any cause regardless of whether the subject withdraws from study therapy or receives another anti-cancer therapy.

Time frame: Up to approximately 13 months

Population: Evaluable population, defined as all participants who entered the maintenance phase and who received at least one dose/have been exposed to any AZD2811 + durvalumab. Only the AZD2811 + durvalumab arm is evaluable.~Due to the early termination of study enrolment, data were not collected up to the intended time frame of 3 years.