A Phase III Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Non Small Cell Lung Cancer (NSCLC) Whose Disease Progressed On or After Prior Anti PD (L)1 Therapy And Platinum Based Chemotherapy
Ceralasertib: Participants will receive ceralasertib oral tablets.
Durvalumab: Participants will receive durvalumab as an intravenous infusion.
Docetaxel: Participants will received docetaxel as an intravenous infusion.
Study summary
This study will assess the efficacy and safety of the combination of ceralasertib and durvalumab versus standard of care docetaxel in patients with locally advanced and metastatic NSCLC after progression on prior anti-PD-(L)1 therapy and platinum-based chemotherapy.
Eligibility
Sex
ALL
Min age
18 Years
Max age
130 Years
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 as determined at a local laboratory.
* 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 either separately or in combination.
* Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 0 or 1.
* Adequate organ function and marrow reserve
* Minimum life expectancy of 12 weeks.
* Body weight \> 30 kg and no cancer-associated cachexia.
* Negative pregnancy test (serum test) for women of childbearing potential (WOCBP).
Exclusion Criteria:
* Participant with mixed SCLC and NSCLC histology.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention.
* Persistent toxicities (CTCAE Grade \> 2) caused by previous anticancer therapy.
* Active or prior documented autoimmune or inflammatory disorders.
* Participants who have received more than one line of prior anti-PD-(L)1, either alone or in any combination.
* Participants:
1. Must not have experienced a toxicity that led to permanent discontinuation of the prior anti-PD(L)1 therapy.
2. All AEs while receiving prior anti-PD(L)1 therapy must have completely resolved.
3. 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.
4. 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, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day.
* Participants who have received more than one prior line of platinum-based chemotherapy in metastatic setting.
* Participants who have received a prior ataxia telangiectasia and Rad3-related protein (ATR) inhibitor.
Primary outcome measure(s)
Overall Survival (OS) — Every 3 months (± 1 week) following objective progression of disease (PD) or treatment discontinuation (up to three years) The superiority of ceralasertib plus durvalumab combination therapy relative to docetaxel will be demonstrated by assessment of OS (HR with 95% CI and p-value) in participants with advanced NSCLC after second- or third-line therapy and without actionable genomic alterations. OS is defined as time from randomisation until the date of death due to any cause.
Trial sites (191)
Facility
City
Region
Status
Research Site
Mobile
Alabama
Research Site
Chandler
Arizona
Research Site
Los Alamitos
California
Research Site
Los Angeles
California
Research Site
Whittier
California
Research Site
Jacksonville
Florida
Research Site
Orlando
Florida
Research Site
Athens
Georgia
Research Site
Atlanta
Georgia
Research Site
Fort Wayne
Indiana
Research Site
Baltimore
Maryland
Research Site
Bethesda
Maryland
Research Site
Rockville
Maryland
Research Site
Hattiesburg
Mississippi
Research Site
St Louis
Missouri
Research Site
Omaha
Nebraska
Research Site
Reno
Nevada
Research Site
Charlotte
North Carolina
Research Site
Winston-Salem
North Carolina
Research Site
Canton
Ohio
Research Site
Cleveland
Ohio
Research Site
Allentown
Pennsylvania
Research Site
York
Pennsylvania
Research Site
Houston
Texas
Research Site
Huntsville
Texas
Research Site
Kingwood
Texas
Research Site
Appleton
Wisconsin
Research Site
Buenos Aires
Argentina
Research Site
Pergamino
Argentina
Research Site
Rosario
Argentina
Research Site
Rosario
Argentina
Research Site
San Juan
Argentina
Research Site
Elizabeth Vale
Australia
Research Site
Lismore
Australia
Research Site
Murdoch
Australia
Research Site
South Brisbane
Australia
Research Site
Wollongong
Australia
Research Site
Charleroi
Belgium
Research Site
Ghent
Belgium
Research Site
Libramont-Chevigny
Belgium
+ 151 more sites — see the full list on the official registry below.
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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