Non-Small Cell Lung Cancer With EGFR Mutation
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGABSK043 in combination with Firmonertinib
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.
Sponsors
Abbisko Therapeutics Co, Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically documented locally advanced or metastatic NSCLC 2. At least 1 measurable lesion as assessed by Investigator as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) 3. Inclusion Criteria Specific to Dose Escalation cohort and Dose Confirmation Cohort：Must has disease progression following treatment with EGFR-TKI in the locally advanced or metastatic setting for locally advanced or metastatic disease Documentation of PDL1 expression positive (TPS/TC≥1%)detected from tumor tissue Inclusion Criteria Specific to Dose expansion Cohort： Must not have received any other prior systemic cancer therapies in the locally advanced/metastatic setting PDL1 expression positive (TPS/TC≥1%) as assessed by central laboratory from tumor tissue 4. Adequate bone marrow reserve and organ function based on local laboratory data . 5. Documented genetic testing reports confirmed the presence of EGFR L858R or EGFR exon 19 del mutations in tumor or plasma ctDNA.
Exclusion criteria
1. 1\. Histological or cytological examinations suggest that NSCLC squamous cells is the predominant histology, or contains small cell lung cancer, neuroendocrine carcinoma, etc. 2. Has a history of interstitial lung disease (ILD)/pneumonitis or active ILD 3. Has spinal cord compression or clinically active central nervous system metastases, defined as symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study 4. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, Grade ≤1 or baseline. 5. Is receiving chronic systemic corticosteroids dosed at \>10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy. 6. Uncontrolled or significant cardiovascular disease 7. Has a known human immunodeficiency virus (HIV) infection that is not well controlled. 8. Any evidence of severe or uncontrolled diseases or other factors which in the Investigator's opinion makes it undesirable for the patients to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of DLT | At the end of Cycle 1 (each cycle is 21 days) | Dose-limiting toxicities |
| AEs | 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. | Adverse events |
| SAEs | 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. | Serious adverse events (SAEs) |
| AESIs | 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. | Adverse events of special interest (AESIs) |
| PFS rate at 12 month | From the time patients receive the first dose of study drug to 12 months，assessed up to 30 months. | Progression-free survival at 12 month |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 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. | Maximum observed concentration |
| AUC | 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. | area under the concentration-time curve area under the concentration-time curve area under the concentration-time curve |
| t1/2 | 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. | elimination half-life |
| Vz/F | 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. | apparent volume of distribution |
| CL/F | 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. | apparent oral clearance |
| Cmax,ss | 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. | maximum observed concentration after multiple doses |
| Cmin,ss | 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. | minimum observed concentration after multiple doses |
| AUCtau,ss | 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. | area under the concentration-time curve after multiple doses |
| AR | 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. | accumulation ratio |
| tmax | 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. | time to maximum observed concentration |
| ORR | 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. | Objective response rate |
| DOR | 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. | Duration of response |
| PFS | 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. | Progression-free survival |
| DCR | 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. | Disease control rate |
| OS | 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. | Overall survival |
| TTP | From date of enrolment #Cycle1 Day1# until disease progression, assessed up to 30 months. | Time to progression |
Countries
China
Contacts
Primary ContactYuan Lu
Backup ContactYinan Lin
Outcome results
None listed