A Phase 1/2, Open-label, Multicenter, FIH Study to Evaluate Safety, Tolerability, PK and Anti-tumor Activity of YH42946

Trial Title: A Phase 1/2, Open-label, Multicenter, FIH Study to Evaluate Safety, Tolerability, PK and Anti-tumor Activity of YH42946

NCT ID: NCT06616766

Condition: NSCLC (non-small Cell Lung Cancer)
Solid Tumor

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

Conditions: Keywords:
YH42946-101

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: YH42946
Description: YH42946
Arm group label: Part 1 and Part 2

Summary: The goal of this YH42946-101 is to evaluate the safety, Tolerability, Pharmacokinetics and anti-tumor activity of YH42946 in patients with locally advanced of metastatic solid tumors with HER2 aberration and EGFR exon 20 insertions.

Detailed description: YH42946 is a novel, orally available tyrosine kinase inhibitor targeting HER2. YH42946 showed potency for diverse HER2 aberrations including HER2 overexpression, amplification, or mutation, as well as EGFR Ex20ins. This is a Phase 1/2, open-label, multicenter, first-in-human study of YH42946. The study has 2 parts. The first part is dose escalation part to identify the maximum tolerated dose. The second part is dose expansion part to select 2 doses for RD selection at the first cohort, after then RD will be determined to ensure its efficacy. Several independent cohorts are planned.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - ECOG performance status 0 or 1 - Estimated life expectancy of at least 3 months - Patients who have progressed on or after all available standard therapies or for whom standard treatment is inappropriate - Mandatory provision of archived or fresh tumor tissue in quantity sufficient to allow for retrospective confirmation of HER2 or EGFR mutation - A patient with a history of brain metastases must have had all lesions treated - Adequate organ function defined as all of the following: - Adequate bone marrow function (within 1 week prior to first administration): Neutrophils≥1.5 x10*9 cells/L (Criteria must be met without the use of Granulocyte-Colony Stimulating Factor (G-CSF) within last week prior to testing.); platelet count≥75 x10*9 cells/L; Hb ≥9g/dL (Criteria must be met without packed red blood cell (pRBC) transfusion within last week prior to testing.) - Adequate hepatic function: Serum bilirubin≤1.5 x upper limit of normal (ULN), and serum transaminase (either aspartate transaminase (AST) or alanine transaminase (ALT)) ≤ 3 x ULN if no demonstrable liver metastases, or otherwise ≤ 5 x ULN if transaminase elevation is attributable to liver metastases (within 1 week prior to first administration) - Adequate renal function: Serum creatinine ≤ 1.5 x ULN or Estimated glomerular filtration rate (eGFR) > 60 mL/min per 1.73 m*2 according to the site's calculation method. [Dose Escalation part only] - Histologically or cytologically confirmed diagnosis of advanced, and/or metastatic non-hematologic malignancy - Documented HER2 or EGFR mutation (HER2 tyrosine kinase domain mutation or EGFR exon 20 insertion, HER2 amplification or overexpression) [Dose Expansion part only] - Patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC HER2 exon 20 insertion (Cohort 1) Exclusion Criteria: - Patient with symptomatic or progressive brain metastases - Known or suspected leptomeningeal disease (LMD) - Uncontrolled spinal cord compression - History of acute coronary syndromes, including myocardial infarction, coronary artery bypass graft, unstable angina, coronary angioplasty or stenting within past 24 weeks - History of or current Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system - Medical, psychiatric, cognitive or other conditions that compromise the patients ability to understand the patient information, to give informed consent, to comply with the study protocol or to complete the study - Any severe concurrent disease or condition (includes active infections, cardiac arrhythmia) that in the judgment of the Investigator would make study participation inappropriate for the patient - History of (non-infectious) interstitial lung disease (ILD) or pneumonitis that required steroids, or any evidence of current ILD or pneumonitis - History of a second primary cancer with the exception of 1. curatively treated non-melanomatous skin cancer, 2. curatively treated cervical or breast carcinoma in situ, or 3. other malignancy with no known active disease present and no treatment administered during the last 2 years - Infection with human immunodeficiency virus (HIV) or active chronic hepatitis B or hepatitis C - Major surgery within 4 weeks prior to the first dose of study treatment

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Seoul National University Hospital

Address:
City: Seoul
Zip: 03080
Country: Korea, Republic of

Contact:
Last name: Do-Youn Oh

Facility:
Name: Severance Hospital, Yonsei University

Address:
City: Seoul
Zip: 120-752
Country: Korea, Republic of

Contact:
Last name: Byoung Chul Cho

Start date: October 31, 2024

Completion date: July 29, 2028

Lead sponsor:
Agency: Yuhan Corporation
Agency class: Industry

Source: Yuhan Corporation

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

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06616766