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 (LATIFY)

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Advanced or Metastatic Non-Small Cell Lung Cancer

Treatments: Drug: Durvalumab; Drug: Ceralasertib; Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT05450692

D533BC00001

2022-000493-26 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 594 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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594 participants in 2 patient groups

Group A: Ceralasertib plus durvalumab combination therapy

Experimental group

Description:

Participants will be administered ceralasertib orally followed by durvalumab administered intravenously.

Treatment:

Drug: Ceralasertib

Drug: Durvalumab

Group B: Docetaxel monotherapy

Active Comparator group

Description:

Participants will be administered docetaxel (standard of care) administered intravenously.

Treatment:

Drug: Docetaxel