Inetetamab in Combination With Pyrotinib in HER2 Mutant or Amplified Advanced Non-small Cell Lung Cancer

NCT05016544 | Unknown Phase 1 DMC

• 1 other identifier: 2021-FXY-191
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label study to evaluate the safety and the efficacy of inetetamab in combination with pyrotinib in patients in HER2 mutant or amplified patients with advanced non-small cell lung cancer

Conditions

Non-small Cell Lung Cancer

Keywords

Non-small Cell Lung Cancer; Inetetamab; Pyrotinib; HER2-activated mutation; HER2-amplification

Outcome Measures

Primary Outcomes (2)

• Dose escalation

  Number of Participants with a Dose-Limiting Toxicity (DLT)

  Up to 21 days after the first dose

• Incidence of adverse events

  Incidence, severity, and serious adverse events (SAEs) based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

  Up to 30 days after the last dose of inetetamab or pyrotinib

Secondary Outcomes (5)

• Objective response rate

  up to12 months

• Disease Control Rate

  up to12 months

• Progression free survival

  24 months

• Overall survival

  36 months

• Investigation on molecular markers associated with the clinical efficacy and the mechanism of drug resistance

  36 months

Study Arms (1)

Inetetamab+Pyrotinib

EXPERIMENTAL

Dose Escalation and Dose Expansion: Inetetamab in combination with Pyrotinib in HER2 mutant or amplified participants with advanced or metastatic NSCLC

Drug: inetetamab; Drug: Pytotinib

Interventions

inetetamab DRUG

All dose levels will receive 8 mg/kg loading dose for cycle 1, followed by 6 mg/kg in subsequent cycles, every 3 weeks.

Inetetamab+Pyrotinib

Pytotinib DRUG

Starting pytotinib Dose of 240mg: Cohort 1: pyrotinib 240mg p.o. d1 to d21, q3w; Cohort 2: pyrotinib 320mg p.o. d1 to d21, q3w; Cohort 3: pyrotinib 400mg p.o. d1 to d21, q3w.

Inetetamab+Pyrotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age over 18;
• Histologically or cytologically documented metastatic NSCLC, HER2 activation amplification or mutation stage IIIB-IV NSCLC patient;
• At least 1 measurable lesion according to RECIST 1.1;
• ECOG score 0 or 1;
• Life expectancy of at least 3 months;
• Within one week before admission, blood routine examination was basically normal:
• hemoglobin ≥90g/L or ≥5.6mmol/L;
• neutrophil count (ANC) ≥ 1.5 × 10 \^ 9 / L;
• platelet count (PLT) ≥ 100 × 10 \^ 9 / L;
• Liver and kidney function tests were basically normal within one week before enrollment;
• total bilirubin (TBIL) ≤ 1.5 × upper limit of normal value (ULN);
• alanine aminotransferase (ALT / AST) ≤ 2.5 × ULN (liver metastasis patients ≤ 5xuln);
• serum creatinine ≤ 1.5 × ULN;
• Partially activated thrombin time(APTT)≤ 1.5 × ULN;
• For fertile women had negative blood pregnancy tests 7 days before screening;

You may not qualify if:

• Patients who have received anti-HER2 monoclonal antibody therapy;
• Have received chemotherapy, biotherapy, targeted therapy, immunotherapy and other anti-tumor therapies within 4 weeks prior to the first use of the study drug including: oral small molecule targeted drugs within 2 weeks prior to the first use of the study drug or within 5 half-lives of known drugs (depending on the time);Radiotherapy was performed within 2 weeks prior to the first administration of the study drug;
• Have received other clinical study drugs within 4 weeks prior to the first study drug administration;
• Patients who underwent major surgery within 4 weeks prior to the first dosing of the study drug(except needle biopsy or significant trauma);
• Those who have been known to have allergic history to the drug components of this regimen;
• Study drugs that had used a CYP3A4 inhibitor, inducer, or a narrow therapeutic window with a CYP3A4-sensitive substrate ,P-ep strong inducer and inhibitor within 14 days before first administration;
• The adverse reactions of previous antitumor therapy have not recovered to CTCAE 5.0 grade 1(Hair loss and other toxicities were excluded for which the researchers judged no safety risk);
• Patients with central nervous system metastasis and clinical symptoms;
• History of immunodeficiency, including positive HIV test, or suffering from other acquired, congenital immunodeficiency diseases, or history of organ transplantation;
• Active hepatitis B (HBV virus titer 1000 copies /ml or 200IU/ml);Hepatitis C virus, syphilis infection;
• Severe heart disease or discomfort, including, but not limited to, the following: complete left bundle branch block or degree atrioventricular block, history of myocardial infarction, angioplasty, coronary artery bridging, patients with prolonged QT/QTc interval at baseline (QTcF men \>450 ms, women \>480ms), significant ventricular arrhythmias (such as ventricular tachycardia), history of heart failure or systolic dysfunction (LVEF \< 50%), cardiac failure, New York College of Cardiology (NYHA) grade II or higher, uncontrolled hypertension (systolic blood pressure \> 180 mmHg ), history or current history of cardiomyopathy that the investigator judged to have an impact on the study;
• Inability to swallow medications orally, or that the investigator determines severely affect gastrointestinal absorption;
• Other malignant tumors in the past 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma or skin squamous cell carcinoma or in situ cervical cancer and/or breast cancer;
• Any history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring steroid treatment, or evidence of clinically active interstitial lung disease;
• Patients with a history of other serious systemic diseases who were judged by the investigator to be unsuitable for clinical trials;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (15)

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MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Li Zhang, MD.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Zhang, MD.

CONTACT

86-20-87343458; zhangli6@mail.sysu.edu.cn

Wenfeng Fang, MD, PhD.

CONTACT

86-020-8734-3894; fangwf@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Sequential assignment by traditional 3+3 dose escalation

Study Record Dates

• First Submitted: August 8, 2021
• First Posted: August 23, 2021
• Study Start: July 28, 2021
• Primary Completion: August 1, 2023
• Study Completion: February 1, 2025
• Last Updated: August 23, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)