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 2s 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 may be demonstrated by:

               1. An FDA-approved device including cobas EGFR Mutation Test v2, therascreen EGFR
                  RGQ PCR Kit, FoundationOne CDx, or MSK-IMPACT, or

               2. A device or test validated and accepted by regulatory health authorities outside
                  the United States for patients enrolled in the trial outside of the United
                  States.

          3. At least one prior treatment with platinum-based chemotherapy. Note: Prior treatment
             with a PD-1/PD-L1 inhibitor is allowed but not required.

          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.

        Exclusion Criteria:

          1. Accelerated Titration Patients Only

             a. Any EGFR tyrosine kinase inhibitors (TKIs), e.g., gefitinib, erlotinib, afatinib,
             and osmertinib, ≤ 8 days or 5x the terminal phase elimination half-lives, whichever is
             longer, prior to the first dose of study drug on C1D1.

          2. Rolling Six, Phase 1 Expansion, and Phase 2a Expansion Patients Only

             Prior treatment with any of the following:

               1. An EGFR-TKI of > 6 months in which the patient derived clinical benefit.

               2. An EGFR exon 20 insertion-targeting drug (e.g., poziotinib, TAK788) for > 2
                  cycles or discontinuation due to progressive disease.

             Note: Patients that discontinued an EGFR 20 insertion-targeting inhibitor for other
             reasons (e.g, intolerability) and have received ≤ 2 cycles of treatment may not be
             excluded upon agreement between the Investigator and Sponsor.

          3. All Patients

             Treatment with any of the following:

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

               2. Limited-field radiotherapy ≤ 7 days or extended-field thoracic radiotherapy < 4
                  weeks of study drug on C1D1.

               3. Major surgery (excluding placement of vascular access) ≤ 4 weeks 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.

          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. Mean resting corrected QT interval (QTc) > 470 msec obtained from three
             electrocardiograms (ECGs).

         10. 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.

         11. 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.

         12. 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.

         13. 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.

         14. Uncontrolled intercurrent illness including, but not limited to, uncompensated
             respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis
             B, hepatitis C, 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.

         15. Active bleeding disorders.

         16. 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:Not yet recruiting
Lead Sponsor:Cullinan Pearl

Trial Keywords

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

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