Non-small Cell Lung Cancer NSCLC
Conditions
Interventions
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 from Day
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1 Participant must be >= 18 years at the time of screening. 2 Histologically or cytologically documented NSCLC that is locally advanced or metastatic according to Version 8 of the IASLC Staging Manual in Thoracic Oncology, at the time of study enrolment. Participants with unknown status are not allowed onto the study. Note: A computed tomography or magnetic resonance imaging scan of the brain at baseline is required for all subjects. 3 Where available, a tissue sample obtained after progression on prior anti-PD-(L)1 therapy and =4 weeks from any prior therapy before the start of study intervention. In addition, the following intervals between the end of the prior treatment and first dose of study intervention must be observed: (a) Minor surgical procedures (as defined by the investigator): 7 post-operative days (b) Major surgery (as defined by the investigator): >= 4 weeks (c) Radiotherapy: >= 4 weeks (participants who receive palliative radiation for non-target tumour lesions need not be subjected to this washout period and can be enrolled immediately). 11 ECOG/WHO performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as >= 10 mm in
Exclusion criteria
Exclusion criteria: 1 Participant with mixed SCLC and NSCLC histology. 2 As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diseases, active infection, active interstitial lung disease/pneumonitis, serious chronic gastrointestinal conditions associated with diarrhoea, psychiatric illness/social situations), history of allogenic organ transplant, which, in the investigator*s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol. 3 Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow a formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of ceralasertib. 4 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 and of low potential risk for recurrence, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy or adequately treated carcinoma in situ without evidence of disease. 5 Brain metastases or spinal cord compression unless the participant is stable (asymptomatic, no evidence of new or emerging brain metastases) and off steroids for at least 14 days prior to start of study treatment. Following radiotherapy and/or surgery, participants with brain metastases must wait 4 weeks following the intervention and must confirm stability with imaging before randomisation. 6 Persistent toxicities (CTCAE Grade > 2) caused by previous anticancer therapy; alopecia and vitiligo are excluded toxicities. Participants with Grade >= 2 neuropathy will be evaluated on a case by-case basis after consultation with the study clinical lead. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study interventions may be included (eg, hearing loss) after consultation with the AstraZeneca study clinical lead. 7 History of ILD/pneumonitis (non-infectious) that required management with steroids. 8 Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn*s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves* disease, rheumatoid arthritis, hypophysitis, uveitis, etc), autoimmune pneumonitis and autoimmune myocarditis). The following are exceptions to this criterion: (a) Participants with vitiligo or alopecia (b) Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement (c) Any chronic skin condition that does not require systemic therapy (d) Participants without active disease in the last 5 years may be included but only after consultation with the study physician (e) Participants with celiac disease controlled by diet alone 9 History of leptomeningeal carcinomatosis. 10 Known active hepatitis infection, positive HCV antibody, HBsAg or anti-HBc at screening. Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HBsAg)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective: To demonstrate superiority of ceralasertib plus durvalumab combination therapy relative to docetaxel by assessment of OS in participants with advanced NSCLC after second- or third-line therapy and without actionable genomic alterations. | — |
Secondary
| Measure | Time frame |
|---|---|
| - To demonstrate superiority of ceralasertib plus durvalumab combination therapy relative to docetaxel by assessment of PFS - To estimate the effectiveness of ceralasertib plus durvalumab*combination therapy relative to*docetaxel by assessment of ORR - To estimate the effectiveness of ceralasertib plus durvalumab combination therapy relative to*docetaxel by assessment of duration of response (DoR) - To estimate the effectiveness of ceralasertib plus durvalumab*combination therapy relative to*docetaxel by assessment of time to response (TTR) - To estimate the effectiveness of ceralasertib plus durvalumab*combination therapy relative to*docetaxel by assessment of disease control rate (DCR) at 18 weeks - To estimate the*effectiveness of*ceralasertib plus durvalumab combination therapy*relative to*docetaxel by*assessment of time to second progression or death (PFS2) - To estimate the effectiveness of ceralasertib plus durvalumab combination therapy relative to docetaxel by assessment of OS at 12 months (OS12) - To assess participant-reported health-related quality of life (QoL) - To assess participant-reported physical functioning in participants treated with ceralasertib plus durvalumab combination therapy relative to docetaxel - To evaluate participant-reported treatment tolerability - To assess the pharmacokinetic (PK) of ceralasertib when administered in combination with durvalumab - To assess the safety and tolerability of ceralasertib plus durvalumab combination therapy as compared with docetaxel | — |
Countries
Netherlands
Outcome results
None listed