Evaluating the safety and effectiveness of YH42946 for advanced solid tumors

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

This study is testing a new oral medication called YH42946 to see if it is safe and effective for people with advanced solid tumors.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 161 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Yuhan Corporation (Industry-sponsored)
• Locations: 8 sites (Fairfax, Virginia and 7 other locations)
• Trial ID: NCT06616766 on ClinicalTrials.gov

What this trial studies

This study aims to assess the safety, tolerability, pharmacokinetics, and anti-tumor activity of YH42946, a novel oral tyrosine kinase inhibitor targeting HER2 and EGFR mutations, in patients with locally advanced or metastatic solid tumors. It consists of two parts: a dose escalation phase to determine the maximum tolerated dose and a dose expansion phase to select effective doses for further evaluation. Patients will be monitored for their response to the treatment and any adverse effects.

Who should consider this trial

Good fit: Ideal candidates include patients with locally advanced or metastatic solid tumors exhibiting HER2 aberrations or EGFR exon 20 insertions who have exhausted standard treatment options.

Not a fit: Patients with tumors that do not have HER2 aberrations or EGFR exon 20 insertions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with specific genetic alterations in their tumors.

How similar studies have performed: Previous studies targeting HER2 and EGFR mutations have shown promising results, indicating potential for success with this novel approach.

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

Where this trial is running

Fairfax, Virginia and 7 other locations

• Next Oncology Virginia — Fairfax, Virginia, United States (Recruiting)
• Seoul National University Bundang Hospital — Seongnam-si, Gyeonggi-do, South Korea (Recruiting)
• The Catholic Univ. of Korea St. Vincent's Hospital — Suwon, Gyeonggi-do, South Korea (Recruiting)
• Chungbuk National University Hospital — Cheongju-si, North Chungcheong, South Korea (Recruiting)
• Seoul National University Hospital — Seoul, South Korea (Recruiting)
• Severance Hospital, Yonsei University — Seoul, South Korea (Recruiting)
• Samsung Medical Center — Seoul, South Korea (Recruiting)
• Asan Medical Center, University of Ulsan — Seoul, South Korea (Recruiting)

Study contacts

• Study coordinator: Yuhan Corporation Clinical Operation Team 1

Conditions NSCLC; Solid Tumor; YH42946-101