Neratinib and Trastuzumab Biosimilar in Patients with HER2 Mutated Advanced Solid Cancers

Phase II Basket Trial to Evaluate Safety and Efficacy of Neratinib, an Irreversible Tyrosine Kinases Inhibitor of EGFR, ERBB2 and ERBB4 Receptors and Trastuzumab Biosimilar (Herzuma®) in Patients with HER2 Mutated Advanced Solid Cancers

Prospective, Basket, Open-label, Multi-dose, Single-arm, Simon's two-stage, Multi-center trial

Study drug : neratinib + herzuma (trastuzumab biosimilar)

Study Overview

• Status: Completed
• Conditions: Metastatic Cancer; HER2 Gene Mutation
• Intervention / Treatment: Drug: Neratinib Maleate

Detailed Description

1. Primary objective Evaluate overall response rate (ORR) in HER2 mutated advanced solid cancer patients based on RECIST v1.1
2. Secondary objectives

(1) Evaluate clinical benefit rate (CBR) (2) Evaluate duration of response (DOR) (3) Evaluate progression free survival (PFS) (4) Evaluate overall survival (OS) (5) Evaluate compliance with oral administration 3) Safety evaluation

1. Evaluate the overall safety of the test drug
2. Evaluate the predefined adverse event (diarrhea)

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who voluntarily decide to participate and give written consent after hearing the explanation of the clinical trial and investigational drugs.
• Adult men and women over 19 years old.
• Histological or cytological confirmed advanced solid tumor and confirmed to have HER2 known oncogenic mutations in tumor DNA by K-master panel test using tumor tissues or circulating tumor DNA in blood.
• Patients having at least 1 or more than 1 measurable lesion according to RECIST v 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0~2.
• Patients whose life expectancy is more than 6 months.
• Metastatic/progressive solid cancer patients who have received one or more than one standard treatment or do not have any treatment option.
• Patients who have agreed to provide plasma/blood samples, the most recent metastatic/progressive tumor sample or new tumor biopsy for gene sequencing and other biomarker analysis.

Exclusion Criteria:

• Patients who received radiotherapy or surgical treatment within 2 weeks prior to the initiation of investigational product.
• Patients having symptomatic brain metastasis who needs treatment. Patients with stable brain metastasis who need no treatment including steroid are eligible
• Inappropriate HER2 mutation (e.g., non-Hot Spot mutation, variant of unknown siginificance, subclonal mutation, premature STOP codon or the Frame Shift mutation).
• Patients having difficulties in swallowing tablets.
• Patients with toxicities of prior treatment which are not recovered to baseline level or ≤ Grade 1.

• Inadequate organ functions:

  1. Hemoglobin (Hemoglobin) < 8 .0g / dL
  2. Absolute neutrophil count (ANC) < 1. 0 x10 ³ per mm³
  3. Platelet count < 100 x10⁹/L (100 ,000/ mm³)
  4. Total bilirubin > 1.5 x upper normal limits (UNL), (exclude Gilbert's syndrome)
  5. Alanine aminotransferase (ALT) or aspartate amino transferase (AST) > 3 x upper normal limits (UNL) (in case of liver and bone metastases > 5 x ULN)
  6. Serum creatinine >1.5 x upper normal limits (UNL) or < eGFR 30 mL/min/1.73 m² 7) Left ventricle ejection fraction <50% by multi-gate obtaining method scan (MUGA) or echocardiogram.

  8) Chronic gastrointestinal disorders of which a main symptom is diarrhea (e.g., Crohn's disease, malabsorption, or grade 2 or more than grade 2 diarrhea according to the NCI CTCAE version 5.0 regardless of etiology).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A arm; Neratinib + herzuma	Drug: Neratinib Maleate; neratinib 240mg po daily; herzuma 8mg/kg (loading) --> 6mg/kg q3w; Other Names: Herzuma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate (ORR)	ORR according to RECIST v1.1	at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical benefit rate, CBR	CR+PR + SD more than 12 weeks	at 6 months
median duration of response, DOR	DOR is related to the quality of life and is one of the methods for evaluating tumor response approved by pharmaceutical regulatory agencies	at 6 months
median progression free survival, PFS	from enrollment to disease progression, death or withdrawal	at 6 months
safety profiles	safety profiles according to CTCAE 4.0	at 6 months

Collaborators and Investigators

• Sponsor: Korea University Guro Hospital
• Collaborators: Korean Cancer Study Group

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2021
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): December 30, 2024

Study Registration Dates

• First Submitted: October 9, 2023
• First Submitted That Met QC Criteria: October 9, 2023
• First Posted (Actual): October 16, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 13, 2025
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Neratinib
• Other Study ID Numbers: AL20-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No