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 (LOTOS)

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

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

• Status: Active, not recruiting
• Conditions: Advanced or Metastatic NSCLC
• Intervention / Treatment: Drug: Ceralasertib; Drug: Durvalumab

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russia
  • Moscow, Russia, 115478
    • Research Site
  • Moscow, Russia, 111123
    • Research Site
  • Moscow, Russia, 115533
    • Research Site
  • Moscow, Russia, 125284
    • Research Site
  • Moscow, Russia, 143423
    • Research Site
  • Nizhny Novgorod, Russia, 603126
    • Research Site
  • Saint Petersburg, Russia, 197758
    • Research Site
  • Saint Petersburg, Russia, 198255
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2023
• Primary Completion (Actual): July 29, 2024
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: June 12, 2023
• First Submitted That Met QC Criteria: July 4, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Neoplasms; Immunotherapy; Lung Diseases; Carcinoma, Non-Small-Cell Lung; Thoracic Neoplasms; Durvalumab; Bronchial Neoplasms; Neoplasms by Site; Lung Neoplasms; Carcinoma, Bronchogenic; Respiratory Tract Neoplasms; ATR inhibitor; Ceralasertib
• Additional Relevant MeSH Terms: Bronchial Diseases; Neoplasms; Lung Diseases; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Diseases; Thoracic Neoplasms; Respiratory Tract Neoplasms; Neoplasms by Site; Bronchial Neoplasms; Carcinoma, Bronchogenic; Antineoplastic Agents, Immunological; Antineoplastic Agents; ceralasertib; durvalumab
• Other Study ID Numbers: AZ-RU-00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No