Clinical Trials /

A Phase 1/2a Trial of CLN-081 in Patients With Non-Small Cell Lung Cancer

NCT04036682

Description:

CLN-081-101 is a Phase 1/2a, open label, multi-center study of CLN-081 in patients with NSCLC (non small cell lung cancer) harboring EGFR (epidermal growth factor receptor) exon 20 insertion mutations, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1/2a Trial of CLN-081 in Patients With Non-Small Cell Lung Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: CLN-081-001
  • NCT ID: NCT04036682

Conditions

  • Non Small Cell Lung Cancer
  • EGFR Exon 20 Mutation

Interventions

DrugSynonymsArms
CLN-081TAS6417Phase 1 Dose Escalation (Accelerated Titration)

Purpose

CLN-081-101 is a Phase 1/2a, open label, multi-center study of CLN-081 in patients with NSCLC (non small cell lung cancer) harboring EGFR (epidermal growth factor receptor) exon 20 insertion mutations, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

Detailed Description

      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.

      CLN-081 will be dosed once daily (QD) and twice daily (BID).
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 Dose Escalation (Accelerated Titration)ExperimentalCLN-081 BID in single patient dose escalation cohorts enrolling NSCLC patients with EGFR exon 20 insertion mutations that either have received or never received prior EGFR TKIs.
  • CLN-081
Phase 1 Dose Escalation (Rolling Six)ExperimentalCLN-081 QD or BID in Rolling Six dose escalation cohorts enrolling NSCLC patients with EGFR exon 20 insertion mutations.
  • CLN-081
Phase 1 Dose Expansion(s)ExperimentalCLN-081 BID in expansion cohorts that may be opened at doses that meet pre-specified efficacy and safety criteria in Rolling Six cohorts.
  • CLN-081
Phase 2a Dose Expansion(s)ExperimentalCLN-081 QD or BID in expansion cohorts that may be opened at doses that meet pre-specified efficacy and safety criteria in Phase 1 Dose Escalation cohorts.
  • CLN-081

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed recurrent, metastatic NSCLC.

          2. Documented EGFR exon 20 insertion mutation demonstrated by a test routinely used by
             each institution and performed in a CLIA-certified or equivalent laboratory.

          3. Prior treatment in the recurrent/metastatic disease setting including:

               1. A platinum-based chemotherapy regimen (or other chemotherapy regimen if
                  platinum-based chemotherapy is contra-indicated)

               2. 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.

          4. Measurable disease by RECIST 1.1.

          5. Age ≥ 18 years.

          6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

          7. Ability to take pills by mouth.

          8. Have the following laboratory values:

               1. 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.

               2. Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome.

               3. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN if due
                  to liver involvement by tumor.

               4. Hemoglobin ≥ 9.0 g/dL.

               5. Platelets ≥ 100 × 109 cells/L.

               6. Absolute neutrophil count ≥ 1.5 ×109 cells/L.

          9. Ability to understand and the willingness to sign a written informed consent document
             and comply with study procedures.

        Exclusion Criteria:

          1. Prior Exon 20 Patients Only

             a. No Prior treatment with an EGFR exon 20 insertion-targeting drug (e.g., poziotinib,
             TAK788, tarloxotinib, JNJ-61186372).

          2. 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).

          3. All Patients

             Treatment with any of the following:

               1. 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

               2. Systemic anticancer treatment (excluding EGFR-TKIs as described above) ≤ 14 days
                  prior to the first dose of study drug on C1D1.

               3. 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.

               4. Immunotherapy ≤ 28 days prior to the first dose of study drug on C1D1.

               5. Major surgery (excluding placement of vascular access) ≤ 28 days of the first
                  dose of study drug on C1D1.

          4. 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.

          5. 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.

          6. Prior therapy with CLN-081.

          7. Known hypersensitivity to CLN-081 or any drugs similar in structure or class.

          8. 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.

          9. 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.

         10. Resting corrected QT interval (QTc) > 470 msec.

         11. 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.

         12. 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.

         13. 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.

         14. 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.

         15. 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.

         16. 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.

         17. For patients with a history of hepatitis C, active infection as defined by a reactive
             HCV antibody test and detectable HCV RNA.

         18. Active bleeding disorders.

         19. Is, in the Investigator's opinion, unable or unwilling to comply with the trial
             procedures.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:All Cohorts: The rate and severity of treatment emergent AEs.
Time Frame:24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Phase 1 Dose Escalation and Dose Expansion Cohorts: ORR
Time Frame:24 months
Safety Issue:
Description:
Measure:Phase 1 Dose Escalation and Dose Expansion Cohorts: DOR (duration of response).
Time Frame:24 months
Safety Issue:
Description:
Measure:Phase 1 Dose Escalation and Dose Expansion Cohorts: DCR (disease control rate)
Time Frame:24 months
Safety Issue:
Description:
Measure:Phase 1 Dose Escalation and Dose Expansion Cohorts: PFS (progression free survival)
Time Frame:24 months
Safety Issue:
Description:
Measure:Phase 1 Dose Escalation and Dose Expansion Cohorts: OS (overall survival)
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Assessment of maximum concentration (Cmax)
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Assessment of area under curve (AUC)
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Assessment of time to maximum concentration (tmax)
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Assessment of terminal half-life (t1/2)
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Assessment of mean residence time (MRT)
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Cullinan Pearl

Trial Keywords

  • NSCLC
  • EGFR
  • Exon 20 insertions
  • CLN-081
  • TAS6417

Last Updated

January 15, 2021