A Study to Investigate Efficacy and Safety of Ceralasertib Plus Durvalumab in Participants Aged ≥ 18 Years With Advanced or Metastatic Non-small Cell Lung Cancer Whose Disease Progressed on or After Prior Anti-PD-(L)1 Therapy and Platinum-based Chemotherapy

Study Overview
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Brief Summary
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A study to investigate efficacy and safety of ceralasertib plus durvalumab in participants aged ≥ 18 years with advanced or metastatic non-small cell lung cancer whose disease progressed on or after prior anti-PD-(L)1 therapy and platinum-based chemotherapy.

Detailed Description
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This is a single-arm study, all participants will be assigned to one treatment group - ceralasertib plus durvalumab combination therapy. Each 28-day cycle will begin with ceralasertib administered orally followed by durvalumab administered intravenously. The objectives of the current single-arm local study are to estimate the efficacy and safety of ceralasertib and durvalumab combination in local population to obtain relevant information for routine clinical practice. The results of this additional study will provide clinical data on efficacy and safety of an innovation drug in the new region - Russian Federation.

Official Title
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A Phase II, Open-label, Multicentre, Non-comparative, Single-arm Local Study of Ceralasertib Plus Durvalumab in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations, and Whose Disease Has Progressed On or After Prior Anti-PD-(L)1 Therapy and Platinum-based Chemotherapy

Conditions
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Advanced or Metastatic NSCLC

Intervention / Treatment
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* Drug: Ceralasertib
* Drug: Durvalumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented NSCLC that is locally advanced or metastatic according to Version 8 of the IASLC Staging Manual in Thoracic Oncology. Documented epidermal growth receptor factor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type status. Documented radiological PD whilst on or after receiving the most recent treatment regimen. Eligible for second- or third-line therapy and must have received an anti-PD-(L)1 therapy and a platinum doublet containing therapy for locally advanced or metastatic NSCLC. Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 0 or 1. Adequate organ function and marrow reserve. Body weight > 30 kg and no cancer-associated cachexia. Exclusion Criteria: Participant with mixed SCLC and NSCLC histology. Brain metastases or spinal cord compression unless the participant is stable and off steroids. Persistent toxicities (CTCAE Grade > 2) caused by previous anticancer therapy. Active or prior documented autoimmune or inflammatory disorders. History of leptomeningeal carcinomatosis. Participants who have received more than one line of prior anti-PD-(L)1. Participants must not have experienced a toxicity that led to discontinuation of the prior anti-PD(L)1 therapy. Participants must not have experienced a Grade ≥ 3 immune-mediated adverse event (imAE) or an immune-related neurologic or ocular AE of any grade while receiving prior anti-PD(L)1 therapy. Participants must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged. Participants who have received more than one prior line of platinum-based chemotherapy in metastatic setting. As judged by the investigator, any evidence of medical condition, which, in the investigator's opinion, makes it undesirable for the participant to participate in the study. Participants who have received a prior ATR inhibitor. Diagnosis of ataxia telangiectasia.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Ceralasertib plus durvalumab combination therapy Participants will be administered orally ceralasertib followed by IV durvalumab each 28 days cycle. | Drug: Ceralasertib<br>* Participants will receive ceralasertib oral tablets.<br>Drug: Durvalumab<br>* Participants will receive durvalumab as an intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Objective response rate (ORR) is defined as the proportion of participants who have a complete response (CR) or partial response (PR) per RECIST 1.1. | At month 6 after the last patient's first dose (approximately 18 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DoR) | DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1. | Up to 30 months | 
| Time to response (TTR) | Time to response (TTR) is defined as the time from the start of treatment until the date of first documented objective response per RECIST 1.1. | Up to 30 months | 
| Disease control rate (DCR) | DCR at 18 weeks is defined as the percentage of participants who have a CR or PR or who have stable disease (SD) for at least 17 weeks per RECIST 1.1. | At month 6 after the last patient's first dose (approximately 18 months). | 
| Progression free survival (PFS) | PFS is defined as time from the start of treatment until progression per Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1). | Up to 30 months | 
| Overall survival (OS) | OS is defined as time from the start of treatment until the date of death due to any cause. | Up to 30 months | 
| Number and percentage of AEs in patients receiving Ceralasertib and Durvalumab combination | The safety and tolerability profile of Ceralasertib and Durvalumab combination will be evaluated using vital signs, laboratory data, electrocardiograms (ECGs), and adverse event data | Up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Neoplasms, Lung Diseases, Carcinoma, Non-Small-Cell Lung, Carcinoma, Bronchogenic, Respiratory Tract Diseases, Bronchial Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Durvalumab, Ceralasertib, ATR inhibitor, Immunotherapy