To assess the efficacy and safety of Almonertinib versus placebo following chemoradiation in patients with stage III unresectable epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC).
This is a randomized, double-blind, placebo-controlled, multicenter, phase III study to assess the efficacy and safety of Almonertinib following chemoradiation in patients with stage III unresectable EGFRm+ NSCLC, including the most common EGFR sensitizing mutations (Ex19Del and L858R), either alone or in combination with other EGFR mutations (e.g., T790M). Chemoradiation may have been given either concurrently or sequentially. Patients whose disease has not progressed following chemoradiation will be randomised within 6 weeks of completion of chemoradiation to receive Almonertinib or placebo in a 2:1 ratio, and treatment will be continued until disease progression, unacceptable toxicity or other discontinuation criteria are met. After progression, patients can be unblinded and may receive open-label Almonertinib for as long as their treating physician considers they are deriving clinical benefit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
150
The initial dose of Almonertinib 110 mg daily can be reduced to 55 mg daily under specific conditions. Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met. The 2:1 ratio (Almonertinib to placebo).
The initial dose of Placebo Almonertinib 110 mg daily can be reduced to 55 mg daily under specific conditions. Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met. The 2:1 ratio (Almonertinib to placebo).
Shandong Cancer Hospital
Ji'nan, Shandong, China
RECRUITINGProgression-free survival (PFS) assessed by IRC (Independent Review Committee)
Progression-free survival (PFS) assessed by IRC (Independent Review Committee) Description: PFS is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on blinded independent central review assessment according to RECIST 1.1.
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.
PFS assessed by INVs (Investigators)
PFS is defined as the time from randomization to progression of tumor as assessed by INVs or death from any cause on study.
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.
Time to CNS PFS assessed by IRC
Defined as earlier event of CNS progression or death based on blinded independent central review assessment according to RECIST 1.1.
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.
Overall survival (OS)
OS is defined as the time from the date of randomization until death due to any cause.
Time frame: From baseline until death due to any cause; up to a maximum of approximately 4 years.
Objective response rate (ORR)
Defined as the number (%) of patients with measurable disease with at least 1 visit response of CR (Complete response) or PR (Partial response) based on blinded independent central review assessment according to RECIST 1.1.
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Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years.
Duration of response (DoR)
Defined as the time from the date of first documented response (i.e., subsequently confirmed) until the date of documented progression or death in the absence of disease progression based on blinded independent central review assessment according to RECIST 1.1.
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years.
Disease control rate (DCR)
Defined as Disease control rate is defined as the percentage of subjects who have a best overall response of CR or PR or SD based on blinded independent central review assessment according to RECIST 1.1.
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years.
Time to death or distant metastases (TTDM)
Defined as the time from the date of randomization until the first date of distant metastasis or date of death in the absence of distant metastasis based on blinded independent central review assessment according to RECIST 1.1
Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years.
Incidence of Adverse Events (AEs)
AEs are graded according to CTCAE v5.0 and recorded in the case report form.
Time frame: From the screening period to 28 days after treatment completion, approximately 4 years.