A Study of VRN110755 in Patients With EGFR-Mutant Non-Small Cell Lung Cancer

NCT07699328 | Recruiting Phase 1 DMC

• 2 other identifiers: VRN110755_012025-523122-40-00
• Study Type: interventional
• Target: 315
• Locations: 10 countries
• Sites: 29

Brief Summary

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.

Conditions

EGFR-Mutant Non-Small Cell Lung Cancer

Keywords

NSCLC; EGFR; Epidermal Growth Factor Receptor; Non-Small Cell Lung Cancer; EGFR Mutation; C797S; EGFR Tyrosine Kinase Inhibitor Resistance

Outcome Measures

Primary Outcomes (9)

• Estimate of Maximum Tolerated Dose (MTD) of VRN110755

  This will be based on dose-limiting toxicities (DLTs) observed during the DLT evaluation period.

  28 days

• Number of participants with dose-limiting toxicities (DLTs) following treatment with VRN110755

  Dose-limiting toxicities will be assessed according to protocol-defined DLT criteria during the DLT evaluation period.

  28 days

• Number of participants experiencing treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events leading to discontinuation

  From first dose until end of study (up to approximately 6 years)

• Number of participants with changes in vital signs from baseline following treatment with VRN110755

  Vital signs include blood pressure, pulse rate, respiratory rate, body temperature, and oxygen saturation.

  From baseline through End of Treatment (up to approximately 6 years)

• Number of participants with changes in laboratory test results from baseline following treatment with VRN110755

  Laboratory evaluations include hematology, clinical chemistry, coagulation, and urinalysis assessments.

  From baseline through End of Treatment (up to approximately 6 years)

• Number of participants with changes in physical examination findings from baseline following treatment with VRN110755

  Physical examinations include complete physical examinations at screening and End of Treatment and symptom-directed physical examinations during study treatment.

  From baseline through End of Treatment (up to approximately 6 years)

• Number of participants with changes in ophthalmologic examination findings from baseline following treatment with VRN110755

  Ophthalmologic examinations include best corrected visual acuity, intraocular pressure, slit-lamp examination, spectral-domain optical coherence tomography (SD-OCT), confrontation visual fields, and fundoscopic examination.

  From baseline through End of Treatment (up to approximately 6 years)

• Number of participants with changes in electrocardiogram (ECG) parameters from baseline following treatment with VRN110755

  Electrocardiogram assessments include 12-lead ECG parameters, including QT interval corrected using Fridericia's formula (QTcF).

  From baseline through End of Treatment (up to approximately 6 years)

• Number of participants with changes in Eastern Cooperative Oncology Group (ECOG) Performance Status from baseline following treatment with VRN110755

  From baseline through End of Treatment (up to approximately 6 years)

Secondary Outcomes (20)

• Plasma PK of VRN110755 - Maximum Plasma Concentration (Cmax)

  Predose and up to 24 hours postdose on protocol-specified pharmacokinetic sampling days.

• Plasma PK of VRN110755 - Minimum Plasma Concentration (Cmin)

  Predose and up to 24 hours postdose on protocol-specified pharmacokinetic sampling days.

• Plasma PK of VRN110755 - Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast)

  Predose and up to 24 hours postdose on protocol-specified pharmacokinetic sampling days.

• Plasma PK of VRN110755 - Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUCτ)

  Predose and up to 24 hours postdose on protocol-specified pharmacokinetic sampling days.

• Plasma PK of VRN110755 - Time to Maximum Plasma Concentration (Tmax)

  Predose and up to 24 hours postdose on protocol-specified pharmacokinetic sampling days.

Study Arms (5)

Phase 1a Dose Escalation

EXPERIMENTAL

Participants with advanced, metastatic, or recurrent EGFR-mutant non-small cell lung cancer (NSCLC) who have experienced disease progression following prior EGFR tyrosine kinase inhibitor (TKI) therapy and harbor activating, resistant, uncommon, or complex EGFR mutations. Participants receive escalating dose levels of VRN110755 to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity and to determine the maximum tolerated dose (MTD).

Drug: VRN110755

Phase 1b Cohort A

EXPERIMENTAL

Participants with EGFR-mutant NSCLC harboring exon 19 deletion or exon 21 L858R mutations and a C797X resistance mutation following progression on first-line third-generation EGFR TKI therapy, including osimertinib, lazertinib, or aumolertinib. Participants receive VRN110755 to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity and to support selection of the recommended Phase 2 dose.

Drug: VRN110755

Phase 1b Cohort B

EXPERIMENTAL

Treatment-naïve participants with NSCLC harboring common EGFR mutations. Participants receive VRN110755 to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity in patients who have not previously received systemic treatment for EGFR-mutant NSCLC.

Drug: VRN110755

Phase 1b Cohort C

EXPERIMENTAL

Participants with NSCLC harboring atypical or uncommon EGFR mutations, including G719X, L861Q, S768I, E709X, R776H, L747S, or combinations thereof, who have previously received at least one prior systemic therapy, including an EGFR TKI, and have no remaining standard treatment options expected to provide clinical benefit. Participants receive VRN110755 to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity.

Drug: VRN110755

Phase 1b Cohort D

EXPERIMENTAL

Treatment-naïve participants with NSCLC harboring atypical EGFR mutations. Participants receive VRN110755 to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity in patients who have not previously received systemic treatment for EGFR-mutant NSCLC.

Drug: VRN110755

Interventions

VRN110755 DRUG

VRN110755 is an investigational highly selective oral EGFR inhibitor supplied as capsules for oral administration. The drug is designed to target activating EGFR mutations and selected resistance mutations, including C797S, in patients with EGFR-mutant NSCLC.

Phase 1a Dose Escalation; Phase 1b Cohort A; Phase 1b Cohort B; Phase 1b Cohort C; Phase 1b Cohort D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• Received an investigational anticancer therapy within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment.
• Unresolved side effects from previous anticancer therapy greater than Grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), except for Grade 2 peripheral neuropathy or alopecia.
• Pregnant or breastfeeding, or planning to become pregnant during the study.
• NSCLC with an EGFR or HER2 exon 20 insertion mutation.
• Another active malignancy within the past 3 years, with the exception of adequately treated cancers considered cured.
• Inadequate bone marrow, kidney, or liver function based on protocol-defined laboratory criteria.
• Active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days before the first dose of study treatment.
• Active hepatitis B or hepatitis C infection, or known human immunodeficiency virus (HIV) infection.
• Receipt of a live vaccine within 4 weeks before the first dose of study treatment.
• Use of strong or moderate cytochrome P450 (CYP) 3A inhibitors or inducers, certain herbal supplements, or other prohibited medications within the protocol-defined washout period.
• Major surgery within 4 weeks before the first dose of study treatment or incomplete recovery from major surgery.
• Receipt of prior anticancer therapy within the protocol-defined washout period, including systemic therapy, immunotherapy, or radiotherapy.
• Symptomatic or uncontrolled central nervous system (CNS) metastases or spinal cord compression requiring increasing doses of corticosteroids. Participants with treated and stable CNS metastases or asymptomatic CNS disease may be eligible.
• Requirement for systemic corticosteroid therapy exceeding the protocol-defined limit.
• Clinically significant cardiovascular disease, including prolonged QT interval, clinically significant arrhythmias, recent myocardial infarction, unstable angina, congestive heart failure, uncontrolled hypertension, reduced left ventricular ejection fraction, or use of medications known to prolong the QT interval.

Sponsors & Collaborators

• Voronoi, Inc: lead

Study Sites (29)

Southern Oncology Clinical Research Unit

Bedford Park, South Australia, 05042, Australia

RECRUITING

Monash Medical Centre Clayton

Clayton, Victoria, 3168, Australia

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

AP-HM Hôpital Nord

Marseille, Bouches-du-Rhône, 13915, France

RECRUITING

Centre Georges François Leclerc

Dijon, Côte-d'Or, 21079, France

RECRUITING

Prince of Wales Hospital

Hong Kong, 999077, Hong Kong

RECRUITING

Queen Mary Hospital

Hong Kong, 999077, Hong Kong

RECRUITING

Hospital Umum Sarawak

Kuching, Sarawak, 93586, Malaysia

RECRUITING

Hospital Kuala Lumpur

Kuala Lumpur, 50586, Malaysia

RECRUITING

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

RECRUITING

Institut Kanser Negara

Putrajaya, 62250, Malaysia

RECRUITING

National Cancer Centre Singapore

Singapore, 168583, Singapore

RECRUITING

Tan Tock Seng Hospital

Singapore, 308433, Singapore

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

RECRUITING

The Catholic University of Korea, St. Vincent's Hospital

Suwon, Gyeonggi-do, 16247, South Korea

RECRUITING

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, 28644, South Korea

RECRUITING

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

ICO Badalona - Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

RECRUITING

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Regional Universitario de Málaga - Hospital Civil

Málaga, 29011, Spain

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

RECRUITING

Taichung Veterans General Hospital

Taichung, 407219, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

Taipei Medical University Hospital

Taipei, 11031, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 112201, Taiwan

RECRUITING

Phramongkutklao Hospital

Thung Phaya Thai, Bangkok Metropolis, 10400, Thailand

RECRUITING

Songklanagarind Hospital Prince of Songkla University

Hat Yai, Changwat Songkhla, 90100, Thailand

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Hongryul Jung, PhD

  Voronoi, Inc

  STUDY DIRECTOR

Central Study Contacts

Somi Lee

CONTACT

00 82 32 219 7849; somi@voronoi.io

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will enroll sequentially into Phase 1a dose-escalation cohorts followed by Phase 1b dose-expansion cohorts and Phase 2 cohorts.

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 13, 2026
• Study Start: March 26, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029
• Last Updated: July 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); MY (4); ES (4); TW (5); TH (2); FR (2); KR (5); CA (1); HK (2); SG (2)