This is an open-label phase 2 study to evaluate the safety, tolerability and preliminary anti-tumour activity of ABSK043 in combination with Firmonertinib in patients with Epidermal Growth Factor Receptor-mutated (EGFRm+) locally advanced or metastatic NSCLC.
This is a Phase II, open-label, multicentre study of ABSK043 administered orally in combination with Firmonertinib to patients with EGFRm+ advanced NSCLC. The study has been designed to allow an investigation of the optimal combination dose and schedule whilst ensuring the safety of patients with intensive safety monitoring. There are two main parts to this study; Part A, dose escalation and Parts B Dose expansion. The expansion part will evaluate the efficacy of ABSK043 in combination with Firmonertinib as first-line treatment for locally advanced or metastatic NSCLC patients with EGFR-mutated at the one or more recommended dose. Dose escalation: • Post-line: Patients with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with systemic treatment Dose Expansion: • First-Line: Patients with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation, and without prior systemic therapy for advanced or metastatic disease.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Two potential dose levels ：400 mg twice daily （BID） and 800 mg BID) of ABSK043 are prespecified and firmonertinib will be administered orally at a fixed dose of 80 mg once daily (QD). Patients in dose escalation cohort will receive the ABSK043, 400 mg BID and firmonertinib 80 mg QD as the starting dose for the combination therapy. Patients in dose confirmation cohort and dose expansion cohort will receive the recommended dose in dose escalation cohort and be evaluated for safety and preliminary anti-tumor activity of the combination therapy. After Cycle 1, patients will continue to receive combination therapy every 21 days until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator decision to discontinue treatment, or end of the study.
Hanhui Cancer Hospital
Hefei, Anhui, China
NOT_YET_RECRUITINGHarbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
NOT_YET_RECRUITINGUnion Hospital Tongji Medical College Huzhong University of Science and Techology
Wuhan, Hubei, China
NOT_YET_RECRUITINGIncidence of DLT
Dose-limiting toxicities
Time frame: At the end of Cycle 1 (each cycle is 21 days)
AEs
Adverse events
Time frame: From the time the patient signs the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of furmonertinib mesylate, whichever occurs first, up to 30 months.
SAEs
Serious adverse events (SAEs)
Time frame: From the time patients sign the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of furmonertinib mesylate, whichever occurs first, up to 30 months.
AESIs
Adverse events of special interest (AESIs)
Time frame: From the time patients sign the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of furmonertinib mesylate, whichever occurs first, up to 30 months.
PFS rate at 12 month
Progression-free survival at 12 month
Time frame: From the time patients receive the first dose of study drug to 12 months，assessed up to 30 months.
Cmax
Maximum observed concentration
Time frame: From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
AUC
area under the concentration-time curve area under the concentration-time curve area under the concentration-time curve
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Jilin Cancer Hospital
Changchun, Jilin, China
NOT_YET_RECRUITINGShanghai Chest Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGTime frame: From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
t1/2
elimination half-life
Time frame: From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
Vz/F
apparent volume of distribution
Time frame: From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
CL/F
apparent oral clearance
Time frame: From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
Cmax,ss
maximum observed concentration after multiple doses
Time frame: From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
Cmin,ss
minimum observed concentration after multiple doses
Time frame: From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
AUCtau,ss
area under the concentration-time curve after multiple doses
Time frame: From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
AR
accumulation ratio
Time frame: From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
tmax
time to maximum observed concentration
Time frame: From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
ORR
Objective response rate
Time frame: From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 30 months.
DOR
Duration of response
Time frame: From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 30 months.
PFS
Progression-free survival
Time frame: From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 30 months.
DCR
Disease control rate
Time frame: From date of enrollment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator decision to discontinue treatment, or end of the study, whichever comes first，assessed up to 30 months.
OS
Overall survival
Time frame: From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 30 months.
TTP
Time to progression
Time frame: From date of enrolment #Cycle1 Day1# until disease progression, assessed up to 30 months.