Study of AZD2811 + Durvalumab in ES-SCLC

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: Durvalumab
* Drug: AZD2811
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Etoposide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD2811 + Durvalumab<br>Induction: Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin & Etoposide) Maintenance: AZD2811 + Durvalumab | Drug: Durvalumab<br>* IV infusions through induction phase. IV infusions through maintenance phase until PD or other discontinuation criteria.<br>* Other names: Imfinzi;Drug: AZD2811<br>* IV infusions through maintenance phase until PD or other discontinuation criteria.<br>Drug: Carboplatin<br>* IV infusions through induction phase if chosen by Investigator.<br>Drug: Cisplatin<br>* IV infusions through induction phase if chosen by Investigator.<br>Drug: Etoposide<br>* IV infusions through induction phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maintenance participants alive and progression free (APF12) per RECIST 1.1 [Efficacy] |  | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maintenance participants alive at 12 months (OS12), 15 months (OS15), and 18 months (OS18) |  | 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 |  | Up to 9 months | 
| Objective response rate (ORR) for all participants using investigator assessments according to RECIST 1.1 |  | Approximately 3 years | 
| Maintenance participants Progression-free survival (PFS) using investigator assessments according to RECIST 1.1 |  | Approximately 3 years | 
| Overall survival (OS) in maintenance participants |  | Approximately 3 years | 
| Assess safety and tolerability profile in terms safety assessments, adverse events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v5.0, and dose modifications | Incidence of adverse events as measured by CTCAE 5.0 | Approximately 3 years | 
| Cmin of durvalumab |  | Predose Maintenance Day 1 of Cycles 5 and 7 (up to approximately 3 years) | 
| Cmax of durvalumab |  | Predose Maintenance Day 1 of Cycles 5 and 7 (up to approximately 3 years) | 
| AZD2811 PK: Pharmacokinetics of AZD2811 and its metabolites by measuring whole blood concentration |  | Approximately 3 years | 
| 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. | The EORTC QLQ-C30 consists of 30 questions that can be combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 6 individual items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global measure of health status. The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual. Quality of life issues are assessed using a four-point scale (1= not at all, 2 = a little, 3 = quite a bit, 4 = very much), apart from two questions which are measured between 1 (Very Poor) to 7 (Excellent). | Approximately 3 years | 
| 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, dysphagis, 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). Scoring will be done according to the EORTC QLQ-C30 Scoring Manual (Fayers et al., 2001). A high score for a symptom scale or single item represents a high level of symptomology or problems. | Approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Extensive Stage Small-Cell Lung Cancer, Carcinoma, Small Cell Lung, Oat Cell Carcinoma of Lung, Oat Cell Lung Cancer, Small Cell Cancer Of The Lung, Small Cell Lung Cancer, SCLC, ES-SCLC