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

August 16, 2021 updated by: Li Zhang, MD, Sun Yat-sen University

A Phase Ib Clinical Study Evaluating the Safety and Efficacy of Inetetamab in Combination With Pyrotinib in HER2 Mutant or Amplified Patients With Advanced Non-small Cell Lung Cancer

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a multi-center, opening, dose-escalating phase Ib clinical trial. The aim of the study is to evaluate the safety and efficacy of inetetamab combined with pyrotinib in the treatment of patients in HER2 mutant or amplified patients with advanced non-small cell lung cancer .Primary endpoint of the study is dose-limiting toxicity dosage and safety. Efficacy indicators including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) are as Secondary endpoint. Up to 48 NSCLC patients will be enrolled the treatment will be performed 3+3 dose-escalation phase I design and expanded to phase II study. A treatment cycle lasts 3 weeks,and the combined medication will be continued until the occurrence of toxicity intolerance,disease progression,or death,or patients refuse to continue participating in this clinical study,or the investigators determine that the medication must be terminated.

The recommended initial consistent dose of inetetamab in groups 1-3 are 8 mg/kg, intravenous infusion for more than 90 minutes, and the maintenance dose is 6 mg/kg.

The oral doses of pyrotinib in groups 1-3 were 240 mg, 320 mg, or 400 mg, respectively.

Safety evaluation will be taken according to hematological toxicity, non-hematological toxicity and National Cancer Institute (NCI)-Common Terminology Criteria (CTC) For Adverse Events (AE) V5.0.

Study Type

Interventional

Enrollment (Anticipated)

48

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-Sen University Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age over 18;
  2. Histologically or cytologically documented metastatic NSCLC, HER2 activation amplification or mutation stage IIIB-IV NSCLC patient;
  3. At least 1 measurable lesion according to RECIST 1.1;
  4. ECOG score 0 or 1;
  5. Life expectancy of at least 3 months;

  6. Within one week before admission, blood routine examination was basically normal:

    1. hemoglobin ≥90g/L or ≥5.6mmol/L;
    2. neutrophil count (ANC) ≥ 1.5 × 10 ^ 9 / L;
    3. platelet count (PLT) ≥ 100 × 10 ^ 9 / L;
    4. Liver and kidney function tests were basically normal within one week before enrollment;
    5. total bilirubin (TBIL) ≤ 1.5 × upper limit of normal value (ULN);
    6. alanine aminotransferase (ALT / AST) ≤ 2.5 × ULN (liver metastasis patients ≤ 5xuln);
    7. serum creatinine ≤ 1.5 × ULN;
    8. Partially activated thrombin time(APTT)≤ 1.5 × ULN;
  7. For fertile women had negative blood pregnancy tests 7 days before screening;
  8. willing to participate and sign the informed consent in person.

Exclusion Criteria:

  1. Patients who have received anti-HER2 monoclonal antibody therapy;
  2. 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;
  3. Have received other clinical study drugs within 4 weeks prior to the first study drug administration;
  4. Patients who underwent major surgery within 4 weeks prior to the first dosing of the study drug(except needle biopsy or significant trauma);
  5. Those who have been known to have allergic history to the drug components of this regimen;
  6. 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;
  7. 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);
  8. Patients with central nervous system metastasis and clinical symptoms;
  9. History of immunodeficiency, including positive HIV test, or suffering from other acquired, congenital immunodeficiency diseases, or history of organ transplantation;
  10. Active hepatitis B (HBV virus titer 1000 copies /ml or 200IU/ml);Hepatitis C virus, syphilis infection;
  11. 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;
  12. Inability to swallow medications orally, or that the investigator determines severely affect gastrointestinal absorption;
  13. 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;
  14. Any history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring steroid treatment, or evidence of clinically active interstitial lung disease;
  15. Patients with a history of other serious systemic diseases who were judged by the investigator to be unsuitable for clinical trials;
  16. Alcohol or drug dependence;
  17. Have a clear history of neurological or mental disorders, including epilepsy or dementia;
  18. Pregnant and/or breastfeeding;
  19. Any other reason the investigator considers the patient is not suitable to participate in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Inetetamab+Pyrotinib
Dose Escalation and Dose Expansion: Inetetamab in combination with Pyrotinib in HER2 mutant or amplified participants with advanced or metastatic NSCLC
Drug: inetetamab
All dose levels will receive 8 mg/kg loading dose for cycle 1, followed by 6 mg/kg in subsequent cycles, every 3 weeks.
Drug: Pytotinib

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose escalation
Time Frame: Up to 21 days after the first dose
Number of Participants with a Dose-Limiting Toxicity (DLT)
Up to 21 days after the first dose
Incidence of adverse events
Time Frame: Up to 30 days after the last dose of inetetamab or pyrotinib
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: up to12 months
Per RECIST v1.1 criteria, the proportion of patients whose best remission was CR or PR accounted for the total number of evaluable patients.
up to12 months
Disease Control Rate
Time Frame: up to12 months
Per RECIST v1.1 criteria, the proportion of patients whose best remission was CR , PR and SD accounted for the total number of evaluable patients.
up to12 months
Progression free survival
Time Frame: 24 months
PFS is defined as the time from the date of first dosing till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).
24 months
Overall survival
Time Frame: 36 months
Overall survival (OS) is defined as the time from the date of first dosing till death due to any cause.
36 months
Investigation on molecular markers associated with the clinical efficacy and the mechanism of drug resistance
Time Frame: 36 months
Using next generation sequencing (NGS) method to detect 22 genes from circulating free DNA (cf-DNA) in patients, periphereal blood sample were collected at baseline, first time tumor efficacy evaluation, and withdrawn study due to disease progression.
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Li Zhang, MD., Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 28, 2021

Primary Completion (Anticipated)

August 1, 2023

Study Completion (Anticipated)

February 1, 2025

Study Registration Dates

First Submitted

August 8, 2021

First Submitted That Met QC Criteria

August 16, 2021

First Posted (Actual)

August 23, 2021

Study Record Updates

Last Update Posted (Actual)

August 23, 2021

Last Update Submitted That Met QC Criteria

August 16, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-FXY-191

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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