A Phase II Multicenter, Open-Label, Single Arm Study to Determine the Efficacy, Safety and Tolerability of AZD2811 and Durvalumab Combination as Maintenance Therapy After Induction with Platinum-Based Chemotherapy Combined with Durvalumab, for the First-Line Treatment of Patients with Extensive Stage Small-Cell Lung Cancer.
Primary objective of this study is to evaluate the efficacy of AZD2811 and durvalumab in patients who have not progressed following induction therapy with platinum-based chemotherapy combined with durvalumab. This is an open-label, single arm study. Patients will be treated in an induction phase with platinum-based induction therapy and durvalumab. At the end of this induction period, participants will be assessed for disease progression, per RECIST v1.1. Participants who have not progressed per RECIST v1.1 at the end of the induction phase will roll over into the maintenance phase of the trial, where patients will commence AZD2811 and durvalumab combination. Participants will be treated with AZD2811 and durvalumab as maintenance therapy until confirmed progressive disease, start of non-protocol defined anticancer therapy, unacceptable toxicity, or withdrawal of consent. If study intervention is permanently discontinued, the participant will remain in the study to be evaluated for safety assessment, as well as for confirmed disease progression and for survival. Targeted population are adult patients (aged ≥18 years) with histologically or cytologically documented extensive disease (American Joint Committee on Cancer Stage (7th edition) IV SCLC \[T any, N any,M1 a/b\]), or T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan. Patients must have WHO/ECOG performance status of 0 or 1. Tumor assessments will be performed at Screening as baseline with follow-up every 6 weeks ± 1 week for the first 36 weeks, and then every 8 weeks ±1 week until confirmed objective disease progression.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
31
IV infusions through induction phase. IV infusions through maintenance phase until PD or other discontinuation criteria.
IV infusions through maintenance phase until PD or other discontinuation criteria.
IV infusions through induction phase if chosen by Investigator.
Research Site
Grand Rapids, Michigan, United States
Research Site
Bydgoszcz, Poland
Research Site
Olsztyn, Poland
Research Site
Poznan, Poland
Maintenance Participants Alive and Progression Free (APF12) Per RECIST 1.1 [Efficacy]
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
Maintenance Participants Alive at 12 Months (OS12), 15 Months (OS15), and 18 Months (OS18)
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
Maintenance Participants Alive and Progression Free at 6 Months (APF6) and 9 Months (APF9) Using Investigator Assessments According to RECIST 1.1
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
Objective Response Rate (ORR) for All Participants Using Investigator Assessments According to RECIST 1.1
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
Maintenance Participants Progression-free Survival (PFS) Using Investigator Assessments According to RECIST 1.1
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IV infusions through induction phase if chosen by Investigator.
IV infusions through induction phase.
Research Site
Cheongju-si, South Korea
Research Site
Jinju, South Korea
Research Site
Seoul, South Korea
Research Site
Seoul, South Korea
Research Site
Seoul, South Korea
Research Site
Seoul, South Korea
...and 2 more locations
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
Overall Survival (OS) in Maintenance Participants
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
AZD2811 PK: Pharmacokinetics of AZD2811 and Its Metabolites by Measuring Whole Blood Concentration
Time frame: Up to Cycle 8 Day 8 (approximately 5 months)
EORTC 30: Health Related Quality of Life Based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Cancer (QLQ-C30) v3.0.
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
EORTC 13: Lung Cancer Specific Quality of Life Based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Lung Cancer (QLQ-LC13) v1.0.
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
EORTC 13: Lung Cancer Specific Quality of Life Based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Lung Cancer (QLQ-LC13) v1.0. Use of Pain Medication (Yes/No)
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