A Phase 2 Clinical Study of Combination Therapy With ABSK043 and Firmonertinib

Trial Title: A Phase 2 Clinical Study of Combination Therapy With ABSK043 and Firmonertinib

NCT ID: NCT06668103

Condition: Non-Small Cell Lung Cancer With EGFR Mutation

Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: ABSK043 in combination with Firmonertinib
Description: 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.
Arm group label: ABSK043 in combination with Firmonertinib

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.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Hanhui Cancer Hospital

Address:
City: Hefei
Country: China

Contact:
Last name: Yueyin Pan

Investigator:
Last name: Yueyin Pan
Email: Principal Investigator

Facility:
Name: Harbin Medical University Cancer Hospital

Address:
City: Harbin
Country: China

Contact:
Last name: Yan Yu

Investigator:
Last name: Yan Yu
Email: Principal Investigator

Facility:
Name: Union Hospital Tongji Medical College Huzhong University of Science and Techology

Address:
City: Wuhan
Country: China

Contact:
Last name: Xiaorong Dong

Investigator:
Last name: Xiaorong Dong
Email: Principal Investigator

Facility:
Name: Jilin Cancer Hospital

Address:
City: Changchun
Country: China

Contact:
Last name: Ying Cheng

Investigator:
Last name: Ying Cheng
Email: Principal Investigator

Facility:
Name: Shanghai Chest Hospital

Address:
City: Shanghai
Country: China

Contact:
Last name: Shun Lu

Investigator:
Last name: Shun Lu
Email: Principal Investigator

Start date: December 30, 2025

Completion date: June 30, 2028

Lead sponsor:
Agency: Abbisko Therapeutics Co, Ltd
Agency class: Industry

Source: Abbisko Therapeutics Co, Ltd

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06668103