To assess the efficacy and safety of Almonertinib versus platinum-based chemotherapy as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutation.
This is a randomized, open-lable, multicenter, phase III study to assess the efficacy and safety of Almonertinib versus platinum-based chemotherapy as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring at least one uncommon EGFR mutation, including L861Q, G719X or S768I. Patients who have not received any systemic treatment to receive Almonertinib or platinum-based chemotherapy in a 1:1 ratio, and treatment will be continued until disease progression, unacceptable toxicity or other discontinuation criteria are met. After progression, patients may receive Almonertinib for as long as their treating physician considers they are deriving clinical benefit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
Almonertinib 165 mg,orally once a day Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met.
Pemetrexed (500mg/m2) plus Carboplatin (AUC5)or Pemetrexed (500mg/m2) plus Cisplatin (75mg/m2) on Day 1 of 21day cycles (every 3 weeks) for 4\~6 cycles, followed by pemetrexed mainten-ance therapy every 3 weeks until disease progress-ssion, unacceptable toxicity or other discontinuation criteria are met.
Sun yat-sen Univerisity Cancer Center
Guangzhou, Guangdong, China
Progression-free survival (PFS) assessed by IRC (Independent Review Committee)
PFS is defined as the time from randomization until the date of objective disease progression or death 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 ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.
PFS assessed by INVs (Investigators)
PFS is defined as the time from randomization until the date of disease progression as assessed by INVs according to RECIST 1.1 or death from any cause on study.
Time frame: Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.
Objective response rate (ORR) assessed by IRC
ORR is defined as the number (%) of patients 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.
Time frame: Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.
Duration of response (DoR) assessed by IRC
DoR is defined as the time from date for first documented response of until the documented response of progression per RECIST 1.1 or death in the absence of progression based on blinded independent central review assessment.
Time frame: Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.
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Disease control rate (DCR) assessed by IRC
DCR is defined as the percentage of patients 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 ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.
Depth of response (DepOR) assessed by IRC
DepOR is defined as the change amount of the sum of the lengths of the longest diameters of the target lesions on blinded independent central review assessment according to RECIST 1.1 in the absence of New Lesions (NLs) or progression of Non-Target Lesions when compared to baseline.
Time frame: Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.
Proportion of patients alive and progression free at 6 months (APF6) assessed by IRC
APF6 is defined as the percentage (%) of patients who were alive and progression free per RECIST 1.1 at 6 months after randomization.
Time frame: Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 6 months post-randomization.
Proportion of patients alive and progression free at 9 months (APF9) assessed by IRC
APF9 is defined as the percentage (%) of patients who were alive and progression free per RECIST 1.1 at 9 months after randomization.
Time frame: Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 9 months post-randomization.
Proportion of patients alive and progression free at 12 months (APF12) assessed by IRC
APF12 is defined as the percentage (%) of patients who were alive and progression free per RECIST 1.1 at 12 months after randomization.
Time frame: Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 12 months post-randomization.
Proportion of patients alive and progression free at 24 months (APF24) assessed by IRC
APF24 is defined as the percentage (%) of patients who were alive and progression free per RECIST 1.1 at 24 months after randomization.
Time frame: Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 24 months post-randomization.
Overall survival (OS)
OS is defined as the time from the date of randomization until death due to any cause.
Time frame: From the date of randomization until death due to any cause; up to a maximum of approximately 3 years.
Percentage of patients alive at 36 months (OS36)
OS36 was defined as the percentage (%) of patients who were alive at 36 months after randomization per the Kaplan-Meier estimate of OS at 36 months.
Time frame: From randomization until death due to any cause, up to a maximum of approximately 3 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 3 years.