A Phase I Study of FCN-411 in Advanced Non-small Cell Lung Cancer Chinese Patients With EGFR Positive Mutation

July 14, 2020 updated by: Ahon Pharmaceutical Co., Ltd.

A Phase I, Multi-center, Open-label, Single-arm, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Anti-tumor Activities of FCN-411 Monotherapy in Advanced Non-small Cell Lung Cancer

This phase I trial with dose-escalation stage and dose-expansion stage is the first-in-human study of FCN-411, a drug being developed for treatment of advanced cancers. The initial purpose of the study is to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of FCN-411 monotherapy in EGFR-positive mutation non-small cell lung cancer chinese patients. The study will also provide early information on how the body handles the drug (pharmacokinetics) and on the anti-tumor activities of FCN-411.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, open, single arm phase I clinical trial to explore the dose of FCN-411 in advanced lung cancer patients with disease progression after standard treatment or unsuitable for standard treatment and to expand the dose in advanced NSCLC patients who failed EGFR-TKI treatment. During the screening period, patients need to provide tumor tissue/ blood samples collected after their disease progression for tumor biomarker detection. In this study, the safety, tolerance and pharmacokinetic characteristics of FCN-411 were observed by dose escalation study and dose expansion study, and the antitumor activity of FCN-411 was preliminarily evaluated to determine maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D). The phase I dose escalation study includes two stages: single dose stage and continuous dose stage; phase I dose expansion study is continuous dose administration.

The research cycle is made up of screening period (day-28-day-1), single administration period (7 days), continuous administration period (every 21 days, evaluated every 6 weeks, until disease progression, intolerable toxicity, death, decision of the investigator or voluntary withdrawal of the patient), end of treatment, EOT) visit, safety follow-up (30 days after the last administration), survival follow-up (survival follow-up every 3 months from the safety follow-up until the end of the study). The end of study is one year after the first administration of the last enrolled patient or the end of treatment (whichever is earlier).

Study Type

Interventional

Enrollment (Anticipated)

90

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
      • Beijing, China, 100021
        • Recruiting
        • Cancer hospital chinese academy fo medical scienced
        • Contact:
        • 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 18 years and older.
  2. Histological or cytological confirmed diagnosed advanced or metastatic NSCLC.
  3. Documentation of disease progression while on previous continuous treatment with first-line EGFR TKI; patients must have confirmation of tumor EGFR activating mutations (exon 19 del, or exon 21 ins) and T790M status by biopsy sample or optical microscopy.
  4. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG).
  5. Have a life expectancy of at least 12 weeks.
  6. Have measurable disease based on RECIST v1.1. Note: previously irradiated not chosen, unless disease progression after irradiation.

  7. Adequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:

    1. Neutrophils (absolute value) ≥ 1.5×10^9/L;
    2. Hemoglobin ≥ 90 g/L;
    3. Platelet ≥ 90×10^9/L;
    4. Serum total bilirubin ≤ 1.5× ULN（for Patients with Gilbert Syndrome, total bilirubin ≤ 3×ULN and bilirubin ≤ 1.5×ULN should be permitted）
    5. Aspartate aminotransferase、alanine aminotransferase ≤ 2.5×ULN; for patients with hepatic metastases, AST、ALT ≤ 5×ULN;
    6. Creatinine < 1.5×ULN creatinine clearance rate≥ 45 mL/min (Cockcroft Gault for calculating)
  8. Female subjects have a negative urine or serum pregnancy.

Exclusion Criteria:

  1. Treatment with any of the following:

    1. Treatment with an EGFR TKI within 14 days or about 5 half-lives, whichever is the longer, of the first dose of study drug;
    2. Any cytotoxic chemotherapy, investigational agents or anticancer drugs for the treatment from a previous treatment regimen within 14 days of the first dose of study treatment;
    3. Major surgery within 4 weeks of the first dose of study treatment;
    4. Systemic irradiation including whole brain irradiation;
    5. Previously treated by EGFR-TKI for T790M (for example Osimertinib).
  2. P-glycoprotein inducers (for example Rifampicin) or inhibitors (for example ritonavir) are required during the study.
  3. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
  4. Meningeal metastases or CNS metastasis received intervention or malignancy related epilepsy; brain metastases without symptom are eligible.

  5. Any serious or uncontrolled systemic disease, including but not limited to:

    1. Uncontrolled hypertension;
    2. Active hemorrhage;
    3. Active infections including hepatitis B, or hepatitis C;
    4. Human immunodeficiency virus positive;
    5. Child Pugh C;
    6. Bullous or exfoliative skin diseases;
    7. Severe malnutrition;
    8. History of keratitis or ulcerative keratitis or dry eye;
    9. Uncontrolled large amount of third interstitial fluid retention;
    10. Other serious diseases or mental disorders or laboratory abnormalities.

  6. Cardiac function and disease are consistent with the following:

    1. QTc> 470 milliseconds from 3 electrocardiograms (ECGs);
    2. Any clinically important abnormalities in rhythm;
    3. Any factors that increase the risk of QTc prolongation;
    4. Congestive heart failure ≥ grade 3 by New York Heart Association (NYHA);
  7. Previous history with interstitial lung disease、drug-induced interstitial lung disease or radiation pneumonitis require hormone therapy, or other active interstitial lung diseases required treatments.

  8. Lung function met one of the following criteria:

    1. Oxygen saturation ≤ 88%;
    2. The first second forced expiratory volume< 50% of the predicted value;
    3. Diffusion capacity for CO < 50% of the predicted value.
  9. Dysphagia, or active digestive system diseases or medical conditions potentially affect FCN-411 absorption.
  10. Hypersensitivity to FCN-411 or similar compounds or excipients.
  11. Pregnant or lactating women.

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: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose escalation cohort of FCN-411
  • FCN-411 will be orally administrated at five sequential dose levels, which are 4 mg, 8 mg, 16 mg, 24 mg, and 32 mg.
  • Patients must be diagnosed with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens).
  • Participants will receive FCN-411 monotherapy once daily (QD) for sequential 21-day cycles.
Drug: FCN-411 Dose-escalation
  • FCN-411 is a pan EGFR inhibitor, which has strong activity against wild type (WT), HER2, HER4 and EGFR sensitive mutations (including but not limited to T790M and L858R mutation).
  • FCN-411 shows significant antitumor activity in a dose-dependent manner in in vivo models of lung cancer, esophageal cancer and pharyngeal squamous cell carcinoma mediated by EGFR.
Other Names:
  • EGFR-TKI
Experimental: Dose expansion cohort of FCN-411
  • FCN-411 will be orally administrated at MTD.
  • Patients must be diagnosed with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens).
  • Participants will receive FCN-411 monotherapy once daily (QD) for sequential 21-day cycles.
Drug: FCN-411 Dose-expansion
  • FCN-411 is a pan EGFR inhibitor, which has strong activity against wild type (WT), HER2, HER4 and EGFR sensitive mutations (including but not limited to T790M and L858R mutation).
  • FCN-411 shows significant antitumor activity in a dose-dependent manner in in vivo models of lung cancer, esophageal cancer and pharyngeal squamous cell carcinoma mediated by EGFR.
Other Names:
  • EGFR-TKI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cmax of FCN-411 following single dose.
Time Frame: PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.
Cmax of FCN-411 following single dose.
PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.
AUC of FCN-411 following single dose.
Time Frame: PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.
AUC of FCN-411 After Single Dosing.
PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.
Cmax of FCN-411 following multiple dosing.
Time Frame: The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.
Cmax of FCN-411 After multiple dosing.
The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.
AUC of FCN-411 following multiple dosing.
Time Frame: The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.
AUC of FCN-411 After Multiple Dosing.
The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.
Tmax of FCN-411 following single dose.
Time Frame: PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.
Tmax of FCN-411 following single dose.
PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.
Tmax of FCN-411 following multiple dosing.
Time Frame: The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.
Tmax of FCN-411 following multiple dosing.
The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.
t1/2 of FCN-411 following single dose.
Time Frame: PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.
t1/2 of FCN-411 following single dose.
PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.
t1/2 of FCN-411 following multiple dosing
Time Frame: The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.
t1/2 of FCN-411 following multiple dosing
The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.

Collaborators and Investigators

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

Sponsor

Ahon Pharmaceutical Co., Ltd.

Collaborators

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

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

Helpful Links

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)

August 1, 2018

Primary Completion (Anticipated)

December 31, 2020

Study Completion (Anticipated)

December 20, 2021

Study Registration Dates

First Submitted

November 14, 2017

First Submitted That Met QC Criteria

February 1, 2018

First Posted (Actual)

February 5, 2018

Study Record Updates

Last Update Posted (Actual)

July 16, 2020

Last Update Submitted That Met QC Criteria

July 14, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FCN001

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

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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