Study of AZD2811 + Durvalumab in ES-SCLC

Phase 2

Active, not recruiting

Conditions: Small-Cell Lung Cancer

Interventions: Drug: Durvalumab
Drug: AZD2811
Drug: Carboplatin
Drug: Cisplatin
Drug: Etoposide

Registration Number: NCT04745689

Lead Sponsor: AstraZeneca

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 31

Inclusion Criteria

Documented evidence of extensive stage SCLC (ES-SCLC)
Participants must be considered suitable to receive an induction platinum-based chemotherapy regimen, combined with durvalumab, as first-line treatment for ES-SCLC
No prior exposure to immune-mediated therapy
Life expectancy ≥12 weeks at Day 1.
ECOG 0 or 1 at enrolment.

Exclusion Criteria

Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy
Has a paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic treatment (systemic steroids or immunosuppressive agents) or has a clinical symptomatology suggesting worsening of PNS
Active infection including tuberculosis, HIV, hepatitis B and C
Active or prior documented autoimmune or inflammatory disorders
Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AZD2811 + Durvalumab	Durvalumab	Induction: Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin \& Etoposide) Maintenance: AZD2811 + Durvalumab
AZD2811 + Durvalumab	AZD2811	Induction: Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin \& Etoposide) Maintenance: AZD2811 + Durvalumab
AZD2811 + Durvalumab	Carboplatin	Induction: Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin \& Etoposide) Maintenance: AZD2811 + Durvalumab
AZD2811 + Durvalumab	Cisplatin	Induction: Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin \& Etoposide) Maintenance: AZD2811 + Durvalumab
AZD2811 + Durvalumab	Etoposide	Induction: Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin \& Etoposide) Maintenance: AZD2811 + Durvalumab

Primary Outcome Measures

Name	Time	Method
Maintenance Participants Alive and Progression Free (APF12) Per RECIST 1.1 [Efficacy]	Up to 12 months	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.

Secondary Outcome Measures

Name	Time	Method
Maintenance Participants Alive at 12 Months (OS12), 15 Months (OS15), and 18 Months (OS18)	Up to 18 months	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.
Maintenance Participants Alive and Progression Free at 6 Months (APF6) and 9 Months (APF9) Using Investigator Assessments According to RECIST 1.1	Up to 9 months	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.
Objective Response Rate (ORR) for All Participants Using Investigator Assessments According to RECIST 1.1	Up to approximately 10 months	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.
Maintenance Participants Progression-free Survival (PFS) Using Investigator Assessments According to RECIST 1.1	Up to approximately 10 months	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.
Overall Survival (OS) in Maintenance Participants	Up to approximately 13 months	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.
AZD2811 PK: Pharmacokinetics of AZD2811 and Its Metabolites by Measuring Whole Blood Concentration	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.	Up to Cycle 10 Day 1, approximately 7 months	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.
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.	Up to Cycle 10 Day 1, approximately 7 months	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.
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)	Up to Cycle 10 Day 1, approximately 7 months	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.