Advanced or Metastatic NSCLC
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGCeralasertib
Participants will receive ceralasertib oral tablets.
DRUGDurvalumab
Participants will receive durvalumab as an intravenous infusion
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | At month 6 after the last patient's first dose (approximately 18 months). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) | Up to 30 months | DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1. |
| Number and percentage of AEs in patients receiving Ceralasertib and Durvalumab combination | Up to 30 months | The safety and tolerability profile of Ceralasertib and Durvalumab combination will be evaluated using vital signs, laboratory data, electrocardiograms (ECGs), and adverse event data |
| Disease control rate (DCR) | At month 6 after the last patient's first dose (approximately 18 months). | 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. |
| Progression free survival (PFS) | Up to 30 months | 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). |
| Overall survival (OS) | Up to 30 months | OS is defined as time from the start of treatment until the date of death due to any cause. |
| Time to response (TTR) | Up to 30 months | 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. |
Countries
Russia
Outcome results
None listed