A Study of VRN101099 in Patients With HER2-Positive Solid Tumors

NCT06806982 | Recruiting Phase 1 DMC

• 1 other identifier: VRN101099_01
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This FIH open-label study aims to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor effect of VRN101099 in patients with HER2-positive solid tumors for whom no standard therapies are available.

Conditions

HER2-positive Solid Tumors

Keywords

HER2

Outcome Measures

Primary Outcomes (5)

• Estimate of Maximum tolerated dose (MTD) of VRN101099

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

  Up to 2 years post first dose administration

• Number of participants with Adverse events (AEs) and Serious Adverse events (SAE) as assessed by Medical Dictionary for Regulatory Activities (MedDRA®).

  Up to 2 years post first dose administration

• Number of patients with changes in ECOG performance status from baseline following treatment with VRN101099

  From Screening to 14 days post last dose

• Number of patients with changes in physical/ophthalmic examination from baseline following treatment with VRN101099

  From Screening to 14 days post last dose

• Number of patients with changes in laboratory tests from baseline following treatment with VRN101099

  From Screening to 14 days post last dose

Secondary Outcomes (19)

• Plasma PK of VRN101099 and Cycle1 Day 1- Cmax

  Blood sampling from pre dose to 24 hours post dose administration on Cycle1 Day 1 and Day 15 (C1D1, C1D15) and pre dose on Cycle 1 Day 8 (C1D8). Each Cycle-28 days. Additionally, on Predose on Cycle 2 Day 1, Cycle 2 Day 8 and Day 1 of subsequent cycles.

• Plasma PK of VRN101099 and Cycle1 Day 1-AUC0-last

  Blood sampling from pre dose to 24 hours post dose administration on Cycle1 Day 1 and Day 15 (C1D1, C1D15) and pre dose on Cycle 1 Day 8 (C1D8). Each Cycle-28 days. Additionally, on Predose on Cycle 2 Day 1, Cycle 2 Day 8 and Day 1 of subsequent cycles.

• Plasma PK of VRN101099 and Cycle1 Day 1-AUC0-Inf

  Blood sampling from pre dose to 24 hours post dose administration on Cycle1 Day 1 and Day 15 (C1D1, C1D15) and pre dose on Cycle 1 Day 8 (C1D8). Each Cycle-28 days. Additionally, on Predose on Cycle 2 Day 1, Cycle 2 Day 8 and Day 1 of subsequent cycles.

• Plasma PK of VRN101099 and Cycle1 Day 1-Tmax

  Blood sampling from pre dose to 24 hours post dose administration on Cycle1 Day 1 and Day 15 (C1D1, C1D15) and pre dose on Cycle 1 Day 8 (C1D8). Each Cycle-28 days. Additionally, on Predose on Cycle 2 Day 1, Cycle 2 Day 8 and Day 1 of subsequent cycles.

• Plasma PK of VRN101099 and Cycle1 Day 1- λz

  Blood sampling from pre dose to 24 hours post dose administration on Cycle1 Day 1 and Day 15 (C1D1, C1D15) and pre dose on Cycle 1 Day 8 (C1D8). Each Cycle-28 days. Additionally, on Predose on Cycle 2 Day 1, Cycle 2 Day 8 and Day 1 of subsequent cycles.

Study Arms (1)

VRN101099

EXPERIMENTAL

VRN101099 capsules will be administered orally as monotherapy once daily over 21-day cycles Dose and frequency of dosing: The planned doses for dose escalation are 80 mg, 160 mg, 240 mg, 320 mg, 400 mg, and 480 mg once daily. Dosage form- Oral capsules

Drug: VRN101099

Interventions

VRN101099 DRUG

Oral capsules

VRN101099

Eligibility Criteria

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

You may qualify if:

• Aged ≥ 18 years (patients in Korea must be aged ≥ 19 years).
• Able to comprehend and willing to sign an informed consent form and to abide by the study requirements and restrictions.
• Has at least 1 evaluable lesion (measurable or non-measurable) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (note: metastatic brain lesions will also be assessed using the Response Assessment in Neuro-Oncology - Brain Metastases \[RANO-BM\] as an exploratory objective).
• Has confirmed HER2-positive or mutated cancer as determined by immunohistochemistry (IHC) staining (IHC 1+, 2+, 3+) or next-generation sequencing (NGS) of tissue or circulating tumor DNA (i.e., evaluation of HER2 copy numbers or mutations) (note: documentation of HER2 status is required prior to Screening;
• In the opinion of the Investigator, is medically confirmed to derive no clinical benefit from other standard therapies.
• In the opinion of the Investigator, has a life expectancy \> 6 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at Screening.
• Women of childbearing potential (WOCBP) who engage in heterosexual intercourse must agree to maintain effective contraception during the study and for up to 6 months after EOT; males whose sexual partners are WOCBP must also agree to maintain effective contraceptive method and should refrain from donating sperm during the study and for up to 6 months after EOT.

You may not qualify if:

• Has a confirmed HER2 exon 20 mutation (in the documented NGS test result).
• Received any IP, cytotoxic chemotherapy, or other anticancer drugs from a previous treatment regimen or clinical study within 3 weeks of the first dose of the study IP (note: Rescreening will be permitted after a washout period of 3 weeks).
• Has been previously treated with systemic anticancer treatment of more than 6 regimens for breast cancer or 3 regimens for other solid tumors (note: local administration of rituximab is allowed but intrathecal methotrexate or concurrent chemoradiotherapy is regarded as systemic therapy).
• Has any AEs from previous chemotherapy that have not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade ≤ 1 (note: Grade ≤ 2 peripheral neuropathy or hair loss is acceptable).
• Is a female who is pregnant, breastfeeding, or (among those of childbearing potential) planning to become pregnant.
• Has a history of other active malignancy within 3 years prior to Screening (note: patients with non-melanoma skin cancer, in situ melanoma, or in situ cervical cancer are permitted to be enrolled).
• Has any of the following laboratory abnormalities during Screening:
• Hematology (note: transfusion or hematopoietic growth factor administration within 14 days prior to Screening test is not allowed):
• White blood cell (WBC) count \< 2.5 × 10 power 9/L
• Absolute neutrophil count (ANC) \< 1500/µL
• Platelets \< 100000/µL
• Hemoglobin \< 9.0 g/dL.
• Clinical chemistry:
• Creatinine clearance \< 60 mL/min according to the Cockroft-Gault equation
• Total bilirubin \> 1.5 × ULN

Sponsors & Collaborators

• Voronoi, Inc: lead

Study Sites (1)

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Study Officials

• Daekwon Kim

  Voronoi, Inc. Chief Executive Officer

  STUDY CHAIR

Central Study Contacts

Rutu Dabhi

CONTACT

+1 201-515-9340; dabhirutu@voronoi.io

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2025
• First Posted: February 4, 2025
• Study Start: February 17, 2025
• Primary Completion: May 1, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)