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.

JRCT ID: jRCT2031220611

Registered date:06/02/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Advanced or Metastatic Non-Small Cell Lung Cancer
• Date of first enrollment: 01/02/2023
• Target sample size: 55
• Countries of recruitment: Argentina,Japan,Australia,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,Germany,Japan,Spain,Japan,France,Japan,UK,Japan,Hong Kong,Japan,India,Japan,Italy,Japan,South Korea,Japan,Netherlands,Japan,Poland,Japan,Rumania,Japan,Serbia,Japan,Taiwan,Japan,USA,Japan
• Study type: Interventional

Intervention(s)

Group A: Ceralasertib plus durvalumab combination therapy
Each 28-day cycle will begin with ceralasertib from Day 1 to Day 7 followed by durvalumab
on Day 8

Group B: Docetaxel monotherapy
Each 21-day cycle will begin with docetaxel on Day 1

Outcome(s)

Primary Outcome

Overall Survival (OS) [ Time Frame: 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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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).

Exclude 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 yearsor more 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 or more 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.

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT05450692