EGFR Activating Mutation, Non-Squamous Non-Small Cell Lung Cancer (NSCLC), MET Positive
Conditions
Keywords
non-squamous NSCLC; MET inhibitor; EGFR inhibitor
Brief summary
To evaluate the efficacy and safety of ASKC202 combined with limertinib as the first-line treatment for locally advanced or metastatic NSCLC
Detailed description
This is a randomized, controlled, multicenter, Phase 3 clinical study designed to evaluate the efficacy and safety of ASKC202 plus limertinib (double-blind Arm A) versus osimertinib (double-blind Arm B) as first-line treatment for patients with locally advanced or metastatic non-squamous NSCLC harboring EGFR sensitizing mutations (19Del or 21 L858R) and MET protein overexpression. In addition, Arm C (open-label) will concurrently evaluate the efficacy and safety of osimertinib plus pemetrexed and cisplatin or carboplatin as first-line treatment for patients with EGFRm+/MET+ locally advanced or metastatic non-squamous NSCLC. Eligible participants will be stratified by EGFR mutation status (19Del vs. L858R) and brain metastasis (yes vs. no) and randomly assigned in a 2:2:1 ratio to Arm A, Arm B, or Arm C. Participants in each arm will receive the corresponding study treatment (21-day cycle) until disease progression, death, intolerable toxicity, or fulfillment of any other protocol-defined treatment discontinuation criterion, whichever occurs first.
Interventions
DRUGASKC202
ASKC202 tablets 200 mg QD
DRUGASKC202 placebo
ASKC202 placebo tablets QD
DRUGosimertinib placebo
osimertinib placebo tablets QD
DRUGosimertinib
osimertinib tablets 80 mg QD
DRUGpemetrexed
pemetrexed 500 mg/m² by intravenous infusion on Day 1 of each 21-day cycle
cisplatin 75 mg/m² or carboplatin (AUC 5) by intravenous infusion on Day 1 of each 21-day cycle for up to 4 cycles
DRUGLimertinib
limertinib tablets 80 mg BID
DRUGlimertinib placebo
limertinib placebo tablets BID
Sponsors
Jiangsu Aosaikang Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Capable of giving signed informed consent. 2. Male or female, at least 18 years of age at the time of ICF signing. 3. Histologically or cytologically confirmed locally advanced or metastatic non-squamous NSCLC, not amenable to curative surgery or radiotherapy. 4. Patients must have untreated advanced NSCLC not amenable to curative surgery or radiotherapy. Prior adjuvant and neo-adjuvant therapies or definitive radiation/chemoradiation are permitted as long as treatment was completed at least 6 months prior to the development of recurrent disease. 5. The tumor harbors EGFR sensitizing mutation (Ex19Del or L858R). 6. MET protein overexpression as determined by central laboratory testing of tumor tissue samples. 7. At least one measurable lesion as assessed by RECIST v1.1. 8. Have adequate organ functions. 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 10. Have an estimated life expectancy ≥ 12 weeks.
Exclusion criteria
1. Known coexistence of other oncogenic driver gene alterations. 2. Prior therapy with an EGFR inhibitor (Patients who have completed the maximum permitted duration of adjuvant therapy and whose disease progressed or recurred ≥12 months after completion of such therapy are eligible for enrollment) or a c-MET-targeted inhibitor. 3. Receipt of any other investigational agent within 4 weeks prior to the first dose of study treatment. 4. Unresolved toxicity of CTCAE Grade ≥2 severity attributed to prior anti-tumor therapy at the time of first dose of study drug. 5. Patients with symptomatic brain metastases or unstable brain metastases. 6. Presence of leptomeningeal disease, brainstem metastases, or spinal cord compression. 7. Prior or concurrent malignancy other than study disease. 8. Inability to swallow oral medication, or any gastrointestinal disease or condition that may significantly impair the absorption of the study drug. 9. Any other serious or uncontrolled acute or chronic medical condition that, in the investigator's judgment, would render the patient unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) by BICR | 3 years | Progression-free survival (PFS) using BICR assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).Progression-free survival was defined as the time from date of randomization until the documentation of objective disease progression (PD) or death from any cause (whichever occurred first). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) by investigator | 3 years | Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Progression-free survival was defined as the time from date of randomization until the documentation of objective disease progression (PD) or death from any cause (whichever occurred first). |
| Overall Survival (OS) | 4 years | The time from the date of randomization to the date of death. |
| Objective Response Rate (ORR) | 3 years | ORR was defined as the percentage of participants with complete response (CR) or partial response (PR). |
| Disease Control Rate (DCR) | 3 years | DCR was defined as the percentage of participants with complete response(CR), partial response(PR) and stable disease(SD). |
| Duration of Response (DoR) | 3 years | Duration of response was defined as the time from when the criteria for CR or PR were first met to the occurrence of an objective disease progression or death. |
| Incidence and severity of treatment-emergent adverse events | 3 years | Assessed by number and severity of adverse events as recorded on the case report form NCI CTCAE v6.0. |
Countries
China
Contacts
CONTACTJiangsu Aosaikang Study Director
Outcome results
None listed