This is an open-label, multi-center, randomized, phase III study. It is aimed to firstly evaluate the effectiveness and safety of almonertinib induction therapy in EGFR-mutated patients with unresectable stage III non-small cell lung cancer, and to evaluate the effectiveness and safety of dynamic MRD guided maintenance therapy with almonertinib after induction therapy with almonertinib and local therapy (radical surgery or radiotherapy) evaluated by MDT diagnostic model. The study includes a screening period (not more than 28 days after the subject with signed informed consent before first medication), treatment period (including induction therapy with almonertinib\\ radical therapy under MDT model\\ consolidation therapy with almonertinib) and follow-up period.
This is an open-label, multi-center, randomized, phase III study. It is aimed to firstly evaluate the effectiveness and safety of almonertinib induction therapy in EGFR-mutated patients with unresectable stage III non-small cell lung cancer, and to evaluate the effectiveness and safety of dynamic MRD guided maintenance therapy with almonertinib after induction therapy with almonertinib and local therapy (radical surgery or radiotherapy) evaluated by MDT diagnostic model. The study includes a screening period (not more than 28 days after the subject with signed informed consent before first medication), treatment period (including induction therapy with almonertinib\\ radical therapy under MDT model\\ consolidation therapy with almonertinib) and follow-up period. Eligible subjects receive 110 mg of almonertinib once a day for 8 consecutive weeks of induction therapy; local treatment (surgical or radical radiotherapy) is selected after MDT assessment. Subjects will be randomly assigned to groups A and B. Stratification factors included EGFR 19deletion or EGFR 21L858R mutation; shedding or non-shedding ctDNA at baseline; radical surgery or radiotherapy under MDT model. Subjects in group A will receive 110 mg of almonertinib once a day for 2 years. Imaging evaluation is conducted every 12 weeks. Subjects in group B will receive almonertinib guided by dynamic MRD monitoring. When ctDNA was positive (MRD+), subjects will receive 110 mg of almonertinib once a day for 12 weeks; when ctDNA was negative (MRD-), subjects will stop almonertinib and be observed for 12 weeks. This model will continue until disease recurrence or metastasis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
192
ctDNA dynamic monitoring guided the Almonertinib treatment group after redical surgery orradiotherapy
Guangdong Lung cancer institute
Guangzhou, Guangdong, China
RECRUITINGAssess the anti-tumor activity by IRC: ORR
The objective response rate (ORR) was assessed by IRC for all eligible subjects after 8 weeks of Almonertinib induction therapy. Until the disease progresses or in the absence of disease progression, the last evaluable data will be recorded in the ORR assessment. However, any CR or PR that occurs after the termination of the study treatment and receiving further anti-tumor therapy will not be included in the ORR calculation.
Time frame: 8 weeks
Assess the anti-tumor activity by IRC: Event free survival (EFS) rate
The 18 months event-free survival period is defined as the time from random to the occurrence of any of the following events within 18 months, whichever occurs first: Tumor progression assessed by IRC according to RECIST 1.1; Tumor recurrence confirmed by IRC, including local recurrence or distant metastasis; Death caused by any cause.
Time frame: 18 months
Assess the anti-tumor activity by investigators: ORR
The objective response rate (ORR) was assessed by investigators for all eligible subjects after 8 weeks of Almonertinib induction therapy. Until the disease progresses or in the absence of disease progression, the last evaluable data will be recorded in the ORR assessment. However, any CR or PR that occurs after the termination of the study treatment and receiving further anti-tumor therapy will not be included in the ORR calculation.
Time frame: 8 weeks
Assess the anti-tumor activity by investigators: Event free survival (EFS)
The 18 months event-free survival period is defined as the time from random to the occurrence of any of the following events within 18 months, whichever occurs first: Tumor progression assessed by investigators according to RECIST 1.1; Tumor recurrence confirmed by investigators, including local recurrence or distant metastasis; Death caused by any cause.
Time frame: 18 months
Event free survival (EFS)
The event-free survival period is defined as the time from random to the occurrence of any of the following events, whichever occurs first: Tumor progression assessed by IRC according to RECIST 1.1; Tumor recurrence confirmed by IRC, including local recurrence or distant metastasis; Death caused by any cause.
Time frame: 2 years
Overall survival (OS)
Overall survival is defined as the time between the date of first administration and the date of death of the subject for any reason.Subjects not dead at the time of the statistical analysis will be truncated at the time when the subject was last known to be alive.
Time frame: more than 2 years
Major pathological response (MPR)
The major pathological response rate is defined as the incidence of tumor regression induced by neoadjuvant therapy with pathological residual tumor ≤10% (only applicable to subjects who have received surgical treatment).
Time frame: 8 weeks
Assess the safety of Almonertinib
To evaluate number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 2 years
Quality of life(QOL) assessed by EORTC QLQ-C30
Quality of Life assessed by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30(EORTC QLQ-C30)
Time frame: 2 years
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