A Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of VRN110755 in Patients With Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer (NSCLC)
This first-in-human, Phase 1/2, multicenter, open-label, non-randomized study evaluates the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of VRN110755, a highly selective oral epidermal growth factor receptor (EGFR) inhibitor, in patients with EGFR-mutant non-small cell lung cancer (NSCLC). The study includes a Phase 1a dose-escalation portion, a Phase 1b dose-expansion portion, and a Phase 2 evaluation. The study is designed to determine the maximum tolerated dose and recommended Phase 2 dose of VRN110755 and to evaluate preliminary and confirmatory antitumor activity in patients with EGFR-mutant NSCLC, including patients with acquired resistance following EGFR tyrosine kinase inhibitor therapy.
• Adults aged 18 years or older (19 years or older in the Republic of Korea).
• Able to understand, sign, and provide written informed consent.
• Histologically or cytologically confirmed advanced, metastatic, or recurrent predominantly nonsquamous non-small cell lung cancer (NSCLC) with a documented epidermal growth factor receptor (EGFR) mutation.
• At least one measurable extracranial lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
• Documented EGFR mutation determined by tumor tissue or liquid biopsy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Able to swallow oral capsules and comply with study procedures.
• Women of childbearing potential must have a negative pregnancy test, must not be breastfeeding, and must agree to use effective contraception during the study and for 7 months after the last safety follow-up visit. Men must agree to use effective contraception during the study and for 6 months after the last safety follow-up visit.
• No appropriate standard treatment options are available or standard treatment is not considered feasible, in the opinion of the investigator.
• Participants must meet the disease-specific eligibility criteria for one of the following study groups:
‣ Phase 1a
• NSCLC with EGFR activating, resistant, uncommon, or complex mutations, including but not limited to exon 19 deletion (Del19), L858R, C797S, or other uncommon EGFR mutations.
∙ Radiographic disease progression following at least 2 cycles of prior EGFR tyrosine kinase inhibitor (TKI) therapy or discontinuation of prior EGFR TKI therapy because of toxicity, with no remaining standard therapy expected to provide clinical benefit.
⁃ Phase 1b - Cohort A
• NSCLC with EGFR exon 19 deletion or L858R mutation plus a C797X resistance mutation following disease progression after first-line treatment with a third-generation EGFR TKI (including osimertinib, lazertinib, or aumolertinib).
⁃ Phase 1b - Cohort B
• Treatment-naïve NSCLC with common EGFR mutations.
⁃ Phase 1b - Cohort C
• NSCLC with atypical or uncommon EGFR mutations (including G719X, L861Q, S768I, E709X, R776H, L747S, or combinations of these mutations) previously treated with at least one systemic therapy, including an EGFR TKI, with no remaining standard therapy expected to provide clinical benefit.
⁃ Phase 1b - Cohort D
• Treatment-naïve NSCLC with atypical EGFR mutations.