Clinical trial NCT05941897: 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
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-07-12
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: At month 6 after the last patient's first dose (approximately 18 months).
Secondary outcomes:
measure: Duration of Response (DoR)
timeFrame: Up to 30 months
measure: Time to response (TTR)
timeFrame: Up to 30 months
measure: Disease control rate (DCR)
timeFrame: At month 6 after the last patient's first dose (approximately 18 months).
measure: Progression free survival (PFS)
timeFrame: Up to 30 months
measure: Overall survival (OS)
timeFrame: Up to 30 months
measure: Number and percentage of AEs in patients receiving Ceralasertib and Durvalumab combination
timeFrame: Up to 30 months
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Nizhny Novgorod
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
Study officials:
References: