A Phase III Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Non Small Cell Lung Cancer (NSCLC) 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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This study will assess the efficacy and safety of the combination of ceralasertib and durvalumab versus standard of care docetaxel in patients with locally advanced and metastatic NSCLC after progression on prior anti-PD-(L)1 therapy and platinum-based chemotherapy.

Detailed Description
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This study will consist of two treatment arms (Groups A and B). Participants will be randomised in a 1:1 ratio to one of the two treatment groups: Group A: Ceralasertib plus durvalumab combination therapy Each 28-day cycle will begin with ceralasertib administered orally followed by durvalumab administered intravenously. Group B: Docetaxel monotherapy Each 21-day cycle will begin with the administration of docetaxel.

Official Title
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A Phase III, Open-label, Randomised, Multicentre Study of Ceralasertib Plus Durvalumab Versus Docetaxel 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: LATIFY

Conditions
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Advanced or Metastatic Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Ceralasertib
* Drug: Durvalumab
* Drug: Docetaxel


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 as determined at a local laboratory. 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 either separately or in combination. Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 0 or 1. Adequate organ function and marrow reserve Minimum life expectancy of 12 weeks. Body weight > 30 kg and no cancer-associated cachexia. Negative pregnancy test (serum test) for women of childbearing potential (WOCBP). Exclusion Criteria: Participant with mixed SCLC and NSCLC histology. History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention. Persistent toxicities (CTCAE Grade > 2) caused by previous anticancer therapy. Active or prior documented autoimmune or inflammatory disorders. Participants who have received more than one line of prior anti-PD-(L)1, either alone or in any combination. Participants: Must not have experienced a toxicity that led to permanent discontinuation of the prior anti-PD(L)1 therapy. All AEs while receiving prior anti-PD(L)1 therapy must have completely resolved. 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. 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, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day. Participants who have received more than one prior line of platinum-based chemotherapy in metastatic setting. Participants who have received a prior ataxia telangiectasia and Rad3-related protein (ATR) inhibitor.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: Ceralasertib plus durvalumab combination therapy<br>Participants will be administered ceralasertib orally followed by durvalumab administered intravenously. | Drug: Ceralasertib<br>* Participants will receive ceralasertib oral tablets.<br>Drug: Durvalumab<br>* Participants will receive durvalumab as an intravenous infusion.<br>|
| Active Comparator: Group B: Docetaxel monotherapy<br>Participants will be administered docetaxel (standard of care) administered intravenously. | Drug: Docetaxel<br>* Participants will received docetaxel as an intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | The superiority of ceralasertib plus durvalumab combination therapy relative to docetaxel will be demonstrated by assessment of OS (HR with 95% CI and p-value) in participants with advanced NSCLC after second- or third-line therapy and without actionable genomic alterations. OS is defined as time from randomisation until the date of death due to any cause. | Every 3 months (± 1 week) following objective progression of disease (PD) or treatment discontinuation (up to three years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS will be defined as the time from the date of randomisation until the date of objective PD. | Up to 3 years | 
| Objective Response Rate (ORR) | ORR is defined as the proportion of participant who have a Complete Response (CR) or Partial Response (PR) per RECIST 1.1. | Up to 3 years | 
| 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 3 years | 
| Time To Response (TTR) | TTR is defined as the time from randomisation until the date of first documented objective response. | Up to 3 years | 
| 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. | At Week 18 | 
| Time to second progression or death (PFS2) | Time from randomisation to PFS2 will be defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death. | Up to 3 years | 
| Overall Survival (OS) at 12 months | OS is defined as time from randomisation until the data of death due to any cause. | At 12 months | 
| Time To Deterioration (TTD) of health-related quality of life (QoL) | TTD is defined as the time from randomisation until the date of first confirmed deterioration. | Up to 3 years | 
| TTD of physical function | TTD in physical functioning is measured by the EORTC QLQ-C30 Physical Function subscale of the EORTC QLQ-C30. | Up to 3 years | 
| Plasma concentrations for ceralasertib plus durvalumab combination therapy | The PK plasma concentration of ceralasertib when administered in combination with durvalumab will be assessed. | Up to 3 years | 
| Number of participants with Adverse Evens (AEs) | The safety and tolerability of ceralasertib plus durvalumab combination therapy as compared with docetaxel will be assessed. | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Durvalumab, Ceralasertib, Docetaxel, Lung cancer