Back to resultsA 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 (LOTOS)
Primary Purpose
Advanced or Metastatic NSCLC
Status
Recruiting
Phase
Phase 2
Locations
Russian Federation
Study Type
Interventional
Intervention
Ceralasertib
Durvalumab
Sponsored by
About this trial
This is an interventional treatment trial for Advanced or Metastatic NSCLC focused on measuring 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
Eligibility Criteria
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.
Sites / Locations
- Research SiteRecruiting
- Research SiteRecruiting
- Research SiteRecruiting
- Research SiteRecruiting
- Research SiteRecruiting
- Research SiteRecruiting
- Research SiteRecruiting
- Research SiteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Group A
Arm Description
Ceralasertib plus durvalumab combination therapy Participants will be administered orally ceralasertib followed by IV durvalumab each 28 days cycle.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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).
Overall survival (OS)
OS is defined as time from the start of treatment until the date of death due to any cause.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05941897
Brief Title
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
Acronym
LOTOS
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 21, 2023 (Actual)
Primary Completion Date
June 29, 2024 (Anticipated)
Study Completion Date
June 29, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced or Metastatic NSCLC
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Description
Ceralasertib plus durvalumab combination therapy Participants will be administered orally ceralasertib followed by IV durvalumab each 28 days cycle.
Intervention Type
Drug
Intervention Name(s)
Ceralasertib
Intervention Description
Participants will receive ceralasertib oral tablets.
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Intervention Description
Participants will receive durvalumab as an intravenous infusion
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
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.
Time Frame
At month 6 after the last patient's first dose (approximately 18 months).
Secondary Outcome Measure Information:
Title
Duration of Response (DoR)
Description
DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1.
Time Frame
Up to 30 months
Title
Time to response (TTR)
Description
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.
Time Frame
Up to 30 months
Title
Disease control rate (DCR)
Description
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.
Time Frame
At month 6 after the last patient's first dose (approximately 18 months).
Title
Progression free survival (PFS)
Description
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).
Time Frame
Up to 30 months
Title
Overall survival (OS)
Description
OS is defined as time from the start of treatment until the date of death due to any cause.
Time Frame
Up to 30 months
Title
Number and percentage of AEs in patients receiving Ceralasertib and Durvalumab combination
Description
The safety and tolerability profile of Ceralasertib and Durvalumab combination will be evaluated using vital signs, laboratory data, electrocardiograms (ECGs), and adverse event data
Time Frame
Up to 30 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
AstraZeneca Clinical Study Information Center
Phone
1-877-240-9479
Email
information.center@astrazeneca.com
Facility Information:
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
111123
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
115533
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
143423
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Research Site
City
Saint Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Research Site
City
St. Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Research Site
City
St. Petersburg
ZIP/Postal Code
198255
Country
Russian Federation
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.Yes,indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Learn more about this trial
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
We'll reach out to this number within 24 hrs