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

Launched by YUHAN CORPORATION · Sep 26, 2024

Keywords

ClinConnect Summary

This clinical trial, called YH42946-101, is studying a new treatment called YH42946 for patients with certain types of advanced solid tumors, specifically those with changes in their HER2 or EGFR genes. The main focus of the study is to check how safe the treatment is, how well it works against tumors, and how the body processes the medication. The trial is currently recruiting participants who are 18 years or older, have a life expectancy of at least three months, and have already received all standard treatments available for their condition.

To be eligible, patients need to provide a sample of their tumor tissue for testing and must have good overall health, particularly in their bone marrow, liver, and kidneys. Those with certain serious health issues, like untreated brain metastases or severe heart problems, cannot participate. If you join the trial, you will be closely monitored by healthcare professionals during the study, and your health and response to the treatment will be carefully evaluated. This trial is an important step in finding new options for patients with challenging forms of cancer.

Gender

ALL

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 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 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