Clinical Trials List
Protocol NumberCLN-081-001
NCT Number(ClinicalTrials.gov Identfier)NCT04036682
2020-03-10 - 2026-05-21
Phase I
Recruiting7
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
A Phase 1/2a, Open-Label, Multi-Center Trial to Assess Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of CLN-081 in Patients With Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations
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Trial Applicant
ICON Clinical Research Pte Ltd
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Sponsor
Cullinan Pearl Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- JIN-YUAN SHIH Division of General Internal Medicine
- 陳冠宇 無
- Jih-Hsiang Lee 無
- 吳尚俊 無
- Chia-Chi Lin 無
- 許嘉林 無
- 林昭文 無
- Chong-Jen Yu 無
- 蔡子修 無
- 廖唯昱 無
- YEN-TING LIN 無
- 徐偉勛 無
- CHAO-CHI HO CHAO-CHI HO 無
- 楊景堯 無
- 廖斌志 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Co-Principal Investigator
- YEN-TING LIN Division of General Internal Medicine
- 吳尚俊 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Non-Small Cell Lung Cancer
Objectives
This is a Phase 1/2a, open-label, multicenter, first-in-human trial to evaluate the safety and tolerability, PK, PD, and preliminary efficacy of CLN-081 in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations.
This trial is divided into three parts: Phase 1 Dose Escalation, Phase 1 Dose Expansion, and Phase 2a Dose Expansion.
The objectives of the dose escalation part are to determine the safety, tolerability, MTD, recommended Phase 2 dose (RP2D), and to evaluate the anti-tumor activity of orally administered CLN-081 monotherapy. Additional objectives are to determine the pharmacokinetic (PK) profile of CLN-081 and CLN-081's activity in patients with known central nervous system (CNS) disease.
Test Drug
CLN-081
Active Ingredient
CLN-081
Dosage Form
Tablet
Dosage
30
Endpoints
Primary Outcome Measures :
All Cohorts: The rate and severity of treatment emergent AEs. [ Time Frame: 24 months ]
All Cohorts: The rate and severity of DLTs. [ Time Frame: 24 months ]
All Cohorts: Incidence of safety laboratory assessment abnormalities. [ Time Frame: 24 months ]
All Cohorts: Incidence of abnormalities in vital signs. [ Time Frame: 24 months ]
Phase 2a Dose Expansion Cohorts: Overall response rate (ORR) [ Time Frame: 24 months ]
Secondary Outcome Measures :
Phase 1 Dose Escalation and Dose Expansion Cohorts: ORR [ Time Frame: 24 months ]
Phase 1 Dose Escalation and Dose Expansion Cohorts: DOR (duration of response). [ Time Frame: 24 months ]
Phase 1 Dose Escalation and Dose Expansion Cohorts: DCR (disease control rate) [ Time Frame: 24 months ]
Phase 1 Dose Escalation and Dose Expansion Cohorts: PFS (progression free survival) [ Time Frame: 24 months ]
Phase 1 Dose Escalation and Dose Expansion Cohorts: OS (overall survival) [ Time Frame: 24 months ]
All Cohorts: Assessment of maximum concentration (Cmax) [ Time Frame: 24 months ]
All Cohorts: Assessment of area under curve (AUC) [ Time Frame: 24 months ]
All Cohorts: Assessment of time to maximum concentration (tmax) [ Time Frame: 24 months ]
All Cohorts: Assessment of terminal half-life (t1/2) [ Time Frame: 24 months ]
All Cohorts: Assessment of mean residence time (MRT) [ Time Frame: 24 months ]
All Cohorts: The rate and severity of treatment emergent AEs. [ Time Frame: 24 months ]
All Cohorts: The rate and severity of DLTs. [ Time Frame: 24 months ]
All Cohorts: Incidence of safety laboratory assessment abnormalities. [ Time Frame: 24 months ]
All Cohorts: Incidence of abnormalities in vital signs. [ Time Frame: 24 months ]
Phase 2a Dose Expansion Cohorts: Overall response rate (ORR) [ Time Frame: 24 months ]
Secondary Outcome Measures :
Phase 1 Dose Escalation and Dose Expansion Cohorts: ORR [ Time Frame: 24 months ]
Phase 1 Dose Escalation and Dose Expansion Cohorts: DOR (duration of response). [ Time Frame: 24 months ]
Phase 1 Dose Escalation and Dose Expansion Cohorts: DCR (disease control rate) [ Time Frame: 24 months ]
Phase 1 Dose Escalation and Dose Expansion Cohorts: PFS (progression free survival) [ Time Frame: 24 months ]
Phase 1 Dose Escalation and Dose Expansion Cohorts: OS (overall survival) [ Time Frame: 24 months ]
All Cohorts: Assessment of maximum concentration (Cmax) [ Time Frame: 24 months ]
All Cohorts: Assessment of area under curve (AUC) [ Time Frame: 24 months ]
All Cohorts: Assessment of time to maximum concentration (tmax) [ Time Frame: 24 months ]
All Cohorts: Assessment of terminal half-life (t1/2) [ Time Frame: 24 months ]
All Cohorts: Assessment of mean residence time (MRT) [ Time Frame: 24 months ]
Inclution Criteria
Inclusion Criteria:
Histologically or cytologically confirmed recurrent, metastatic NSCLC.
Documented EGFR exon 20 insertion mutation demonstrated by a test routinely used by each institution and performed in a CLIA-certified or equivalent laboratory.
Prior treatment in the recurrent/metastatic disease setting including:
A platinum-based chemotherapy regimen (or other chemotherapy regimen if platinum-based chemotherapy is contra-indicated)
Any other approved standard therapy that is available to the patient, unless this therapy is contraindicated, intolerable to the patient, or is declined by the patient. In the case of a patient declining such therapy, documentation that the patient has been informed and declined should be documented in the medical record.
Measurable disease by RECIST 1.1.
Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Ability to take pills by mouth.
Have the following laboratory values:
Serum creatinine < 1.5 × ULN or if higher than normal range, calculated creatinine clearance (CrCl) must be ≥ 50 mL/min/1.73 m2 (by Cockroft-Gault formula); actual body weight must be used for CrCl unless BMI > 30 kg/m2 then lean body weight must be used.
Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome.
Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN if due to liver involvement by tumor.
Hemoglobin ≥ 9.0 g/dL.
Platelets ≥ 100 × 109 cells/L.
Absolute neutrophil count ≥ 1.5 ×109 cells/L.
Ability to understand and the willingness to sign a written informed consent document and comply with study procedures.
Histologically or cytologically confirmed recurrent, metastatic NSCLC.
Documented EGFR exon 20 insertion mutation demonstrated by a test routinely used by each institution and performed in a CLIA-certified or equivalent laboratory.
Prior treatment in the recurrent/metastatic disease setting including:
A platinum-based chemotherapy regimen (or other chemotherapy regimen if platinum-based chemotherapy is contra-indicated)
Any other approved standard therapy that is available to the patient, unless this therapy is contraindicated, intolerable to the patient, or is declined by the patient. In the case of a patient declining such therapy, documentation that the patient has been informed and declined should be documented in the medical record.
Measurable disease by RECIST 1.1.
Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Ability to take pills by mouth.
Have the following laboratory values:
Serum creatinine < 1.5 × ULN or if higher than normal range, calculated creatinine clearance (CrCl) must be ≥ 50 mL/min/1.73 m2 (by Cockroft-Gault formula); actual body weight must be used for CrCl unless BMI > 30 kg/m2 then lean body weight must be used.
Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome.
Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN if due to liver involvement by tumor.
Hemoglobin ≥ 9.0 g/dL.
Platelets ≥ 100 × 109 cells/L.
Absolute neutrophil count ≥ 1.5 ×109 cells/L.
Ability to understand and the willingness to sign a written informed consent document and comply with study procedures.
Exclusion Criteria
Exclusion Criteria:
Prior Exon 20 Patients Only
a. No Prior treatment with an EGFR exon 20 insertion-targeting drug (e.g., poziotinib, TAK788, tarloxotinib, JNJ-61186372).
Rolling Six, Phase 1 Expansion, and Phase 2a Expansion Patients Only
a. Prior treatment with an EGFR exon 20 insertion-targeting drug (e.g., poziotinib, TAK788, tarloxotinib, JNJ-61186372).
All Patients
Treatment with any of the following:
An EGFR tyrosine kinase inhibitors (TKIs) ≤ 8 days or 5x the terminal phase elimination half-lives, whichever is longer, prior to the first dose of study drug on C1D1
Systemic anticancer treatment (excluding EGFR-TKIs as described above) ≤ 14 days prior to the first dose of study drug on C1D1.
Radiotherapy < 28 days and palliative radiation ≤ 14 days prior to the first dose of study drug on C1D1. If irradiated, lesions must have demonstrated clear-cut progression prior to to being eligible for evaluation as target lesions.
Immunotherapy ≤ 28 days prior to the first dose of study drug on C1D1.
Major surgery (excluding placement of vascular access) ≤ 28 days of the first dose of study drug on C1D1.
Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment, except for alopecia and skin pigmentation. Patients with chronic, but stable Grade 2 toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.
Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, treated with surgery and/or radiation, and has been stable without requiring escalating corticosteroids or anti-convulsant medications for at least four weeks prior to the first dose of study drug on C1D1.
Prior therapy with CLN-081.
Known hypersensitivity to CLN-081 or any drugs similar in structure or class.
Cardiac conditions as follows: Patient has a history of congestive heart failure (CHF) Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment.
Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
Resting corrected QT interval (QTc) > 470 msec.
Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function, such as inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.
Have any condition or illness that, in the opinion of the investigator, might compromise patient safety or interfere with the evaluation of the safety of the drug.
Pregnant or lactating women; women of child-bearing potential (WOCBP) must have a negative serum pregnancy test ≤ 7 days prior to receiving study drug on C1D1. WOCBP and males with partners of child-bearing potential must agree to use adequate birth control throughout their participation and for six months following the last dose of study treatment.
History of another primary malignancy ≤ 2 years prior to starting study drug on C1D1, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
Uncontrolled intercurrent illness including, but not limited to, uncompensated respiratory, cardiac, hepatic, or renal disease, active infection (including HIV and active clinical tuberculosis), or renal transplant; ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements.
For patients with a history of hepatitis B, active infection as defined by a positive HBsAg test and detectable HBV DNA. Patients ineligible due to detectable levels of HBV DNA at baseline may be rescreened for enrollment if their HBV DNA levels become undetectable after treatment with antiviral agents, and upon agreement between the investigator and Sponsor.
For patients with a history of hepatitis C, active infection as defined by a reactive HCV antibody test and detectable HCV RNA.
Active bleeding disorders.
Is, in the Investigator's opinion, unable or unwilling to comply with the trial procedures.
Prior Exon 20 Patients Only
a. No Prior treatment with an EGFR exon 20 insertion-targeting drug (e.g., poziotinib, TAK788, tarloxotinib, JNJ-61186372).
Rolling Six, Phase 1 Expansion, and Phase 2a Expansion Patients Only
a. Prior treatment with an EGFR exon 20 insertion-targeting drug (e.g., poziotinib, TAK788, tarloxotinib, JNJ-61186372).
All Patients
Treatment with any of the following:
An EGFR tyrosine kinase inhibitors (TKIs) ≤ 8 days or 5x the terminal phase elimination half-lives, whichever is longer, prior to the first dose of study drug on C1D1
Systemic anticancer treatment (excluding EGFR-TKIs as described above) ≤ 14 days prior to the first dose of study drug on C1D1.
Radiotherapy < 28 days and palliative radiation ≤ 14 days prior to the first dose of study drug on C1D1. If irradiated, lesions must have demonstrated clear-cut progression prior to to being eligible for evaluation as target lesions.
Immunotherapy ≤ 28 days prior to the first dose of study drug on C1D1.
Major surgery (excluding placement of vascular access) ≤ 28 days of the first dose of study drug on C1D1.
Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment, except for alopecia and skin pigmentation. Patients with chronic, but stable Grade 2 toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.
Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, treated with surgery and/or radiation, and has been stable without requiring escalating corticosteroids or anti-convulsant medications for at least four weeks prior to the first dose of study drug on C1D1.
Prior therapy with CLN-081.
Known hypersensitivity to CLN-081 or any drugs similar in structure or class.
Cardiac conditions as follows: Patient has a history of congestive heart failure (CHF) Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment.
Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
Resting corrected QT interval (QTc) > 470 msec.
Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function, such as inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.
Have any condition or illness that, in the opinion of the investigator, might compromise patient safety or interfere with the evaluation of the safety of the drug.
Pregnant or lactating women; women of child-bearing potential (WOCBP) must have a negative serum pregnancy test ≤ 7 days prior to receiving study drug on C1D1. WOCBP and males with partners of child-bearing potential must agree to use adequate birth control throughout their participation and for six months following the last dose of study treatment.
History of another primary malignancy ≤ 2 years prior to starting study drug on C1D1, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
Uncontrolled intercurrent illness including, but not limited to, uncompensated respiratory, cardiac, hepatic, or renal disease, active infection (including HIV and active clinical tuberculosis), or renal transplant; ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements.
For patients with a history of hepatitis B, active infection as defined by a positive HBsAg test and detectable HBV DNA. Patients ineligible due to detectable levels of HBV DNA at baseline may be rescreened for enrollment if their HBV DNA levels become undetectable after treatment with antiviral agents, and upon agreement between the investigator and Sponsor.
For patients with a history of hepatitis C, active infection as defined by a reactive HCV antibody test and detectable HCV RNA.
Active bleeding disorders.
Is, in the Investigator's opinion, unable or unwilling to comply with the trial procedures.
The Estimated Number of Participants
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Taiwan
8 participants
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Global
90 participants
