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

Abbisko Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Non-Small Cell Lung Cancer With EGFR Mutation

Treatments: Drug: ABSK043 in combination with Firmonertinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06668103

ABSK043-202

Details and patient eligibility

About

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.

Full 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.

Enrollment: 54 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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54 participants in 1 patient group

ABSK043 in combination with Firmonertinib

Experimental group

Description:

This is an open-label phase 2 study with an escalation part and an expansion part. * Escalation part: Previously treated patients with EGFR Mutated NSCLC will be enrolled. * Dose escalation cohort: up to 12 patients; * Dose confirmation cohort: at least 3 patients, and up to 12 patients. * Expansion part: * Dose expansion cohort: up to 30 treatment-naïve patients with EGFR Mutated NSCLC are expected to be enrolled.

Treatment:

Drug: ABSK043 in combination with Firmonertinib