Clinical trial NCT05450692: 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
Official title: A Phase III, Open-label, Randomised, Multicentre Study of Ceralasertib Plus Durvalumab Versus Docetaxel 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: LATIFY
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Advanced or Metastatic Non-Small Cell Lung Cancer
Keywords: Durvalumab
Ceralasertib
Docetaxel
Lung cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2022-07-11
Enrollment: 594
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: This study will consist of two treatment arms (Groups A and B).

Participants will be randomised in a 1:1 ratio to one of the two treatment groups:

* Group A: Ceralasertib plus durvalumab combination therapy Each 28-day cycle will begin with ceralasertib administered orally followed by durvalumab administered intravenously.
* Group B: Docetaxel monotherapy Each 21-day cycle will begin with the administration of docetaxel.

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 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 outcomes:
measure: Overall Survival (OS)
timeFrame: Every 3 months (± 1 week) following objective progression of disease (PD) or treatment discontinuation (up to three years)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to 3 years
measure: Objective Response Rate (ORR)
timeFrame: Up to 3 years
measure: Duration of Response (DoR)
timeFrame: Up to 3 years
measure: Time To Response (TTR)
timeFrame: Up to 3 years
measure: Disease Control Rate (DCR)
timeFrame: At Week 18
measure: Time to second progression or death (PFS2)
timeFrame: Up to 3 years
measure: Overall Survival (OS) at 12 months
timeFrame: At 12 months
measure: Time To Deterioration (TTD) of health-related quality of life (QoL)
timeFrame: Up to 3 years
measure: TTD of physical function
timeFrame: Up to 3 years
measure: Plasma concentrations for ceralasertib plus durvalumab combination therapy
timeFrame: Up to 3 years
measure: Number of participants with Adverse Evens (AEs)
timeFrame: Up to 3 years
Other outcomes:
Locations:
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state: Alabama
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city: Los Alamitos
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city: Freiburg
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country: Poland
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country: Romania
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country: Serbia
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country: Spain
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city: Barcelona
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country: Spain
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city: Barcelona
country: Spain
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city: Castello de la Plana
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city: Cordoba
country: Spain
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city: Hospitalet deLlobregat
country: Spain
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country: Spain
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country: Spain
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country: Spain
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country: Spain
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country: Spain
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city: Pozuelo de Alarcon
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city: Sabadell
country: Spain
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country: Spain
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country: Spain
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country: Taiwan
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city: Taichung
country: Taiwan
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country: Taiwan
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city: Taipei City
country: Taiwan
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city: Taoyuan City
country: Taiwan
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city: Yunlin
country: Taiwan
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city: Guildford
country: United Kingdom
facility: Research Site
city: Stevenage
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
city: Wirral
country: United Kingdom
facility: Research Site
Study officials:
References: