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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

Phase 2
Active, not recruiting
Conditions
Advanced or Metastatic NSCLC
Interventions
Registration Number
NCT05941897
Lead Sponsor
AstraZeneca
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
39
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Group ACeralasertibCeralasertib plus durvalumab combination therapy Participants will be administered orally ceralasertib followed by IV durvalumab each 28 days cycle.
Group ADurvalumabCeralasertib plus durvalumab combination therapy Participants will be administered orally ceralasertib followed by IV durvalumab each 28 days cycle.
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
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.

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.

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.

Number and percentage of AEs in patients receiving Ceralasertib and Durvalumab combinationUp 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

Trial Locations

Locations (1)

Research Site

🇷🇺

St. Petersburg, Russian Federation

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