RecruitingPhase 1Phase 2NCT06616766

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

A Phase 1/2, Open-label, Multicenter, FIH Study to Evaluate the Safety, Tolerability, PK and Anti-tumor Activity of YH42946 in Patients With Locally Advanced or Metastatic Solid Tumors With HER2 Aberration and EGFR Exon 20 Insertion

Sponsor

Yuhan Corporation

Enrollment

161 participants

Start Date

Oct 2, 2024

Study Type

INTERVENTIONAL

Conditions

Solid Tumor NSCLC (Non-small Cell Lung Cancer)

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria14

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 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 Criteria14

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
curatively treated non-melanomatous skin cancer,
curatively treated cervical or breast carcinoma in situ, or
other malignancy with no known active disease present and no treatment administered during the last 2 years
Infection with human immunodeficiency virus (HIV) or prior hepatitis B or active chronic hepatitis B or active hepatitis C
Major surgery within 4 weeks prior to the first dose of study treatment