Clinical Trials /

Phase I/II Study of CK-101 in NSCLC Patients and Other Advanced Solid Tumors

NCT02926768

Description:

CK-101 is a novel, potent, small molecule tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral CK-101; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral CK-101; to assess the safety and efficacy of CK-101 in treatment-naive NSCLC patients known to have activating EGFR mutations and previously treated NSCLC patients known to have the T790M EGFR mutation.

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

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II Study of CK-101 in NSCLC Patients and Other Advanced Solid Tumors
  • Official Title: A Phase I/II, Open-Label, Safety, Pharmacokinetic and Efficacy Study of Ascending Doses of Oral CK-101 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CK-101-101
  • NCT ID: NCT02926768

Conditions

  • Lung Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Lung Diseases
  • Adenocarcinoma

Interventions

DrugSynonymsArms
CK-101Daily dose of CK-101

Purpose

CK-101 is a novel, potent, small molecule tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral CK-101; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral CK-101; to assess the safety and efficacy of CK-101 in treatment-naive NSCLC patients known to have activating EGFR mutations and previously treated NSCLC patients known to have the T790M EGFR mutation.

Detailed Description

      This is a first-in-human, two-part, open-label, safety, pharmacokinetic, and efficacy study
      of oral CK-101 administered daily in ascending doses in patients with advanced solid tumor
      cancer, followed by a Phase 2 portion at the recommended Phase 2 dose (RP2D) in previously
      treated non-small cell lung cancer (NSCLC) patients who have documented evidence of EGFR
      T790M mutation and have failed treatment with a first-line EGFR inhibitor.
    

Trial Arms

NameTypeDescriptionInterventions
Daily dose of CK-101ExperimentalDaily oral dose of CK-101
  • CK-101

Eligibility Criteria

        Inclusion Criteria:

          -  Measureable disease according to RECIST Version 1.1

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Minimum age of 18 years

          -  Adequate hematological, hepatic and renal function

          -  Written consent on an Institutional Review Board-approved informed consent form prior
             to any study-specific evaluation

          -  Histologically or cytologically confirmed diagnosis of one of the following:

               1. Metastatic or unresectable locally advanced NSCLC with documented evidence that
                  the tumor harbors one of the two common EGFR mutations known to be associated
                  with EGFR tyrosine kinase inhibitor (TKI) sensitivity (exon 19 deletion, L858R),
                  either alone or in combination with other EGFR mutations, determined by PCR-based
                  testing of the tumor tissue or plasma sample, and without prior exposure to an
                  EGFR-TKI therapy; OR

               2. Metastatic or unresectable locally advanced NSCLC:

                    1. with documented evidence that the tumor harbors an EGFR mutation known to be
                       associated with EGFR TKI sensitivity (including G719X, exon 19 deletion,
                       L858R, L861Q); and

                    2. with evidence of radiological disease progression while on a previous
                       continuous treatment with a first-generation EGFR TKI. In addition, other
                       lines of therapy may have been given. All patients must have evidence of
                       radiological disease progression on or following the last treatment
                       administered; and

                    3. with documented evidence of EGFR T790M mutation determined by PCR-based
                       testing of the tumor tissue or plasma sample following disease progression
                       on most recent treatment regimen (irrespective of whether this is EGFR TKI
                       or chemotherapy).

        Exclusion Criteria:

          -  Active second malignancy or other prior malignancy treated with chemotherapy less than
             or equal to 6 months prior to treatment with CK-101

          -  History of, or evidence of clinically active, interstitial lung disease

          -  Brain metastases unless asymptomatic, stable and not requiring steroids for at least 2
             weeks

          -  Treatment with prohibited medications

          -  Any toxicity related to prior treatment must have resolved to Grade 1 or less, with
             the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy

          -  Certain cardiac abnormalities or history

          -  Non-study related surgical procedures less than or equal to 14 days prior to CK-101
             administration

          -  Females who are pregnant or breastfeeding.

          -  Refusal to use adequate contraception for fertile patients (females and males)

          -  Presence of any serious or unstable concomitant systemic disorder incompatible with
             the clinical study

          -  Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
             swallow the formulated product or previous significant bowel resection
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Incidence of dose-limiting toxicities (DLTs)
Time Frame:From baseline (first dose) to 28 days after last dose, expected average 6 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Phase II: Evaluation of tumor response based on disease control rate as assessed by RECIST 1.1
Time Frame:From baseline (first dose) until disease progression or withdrawal from study, expected average 10 months
Safety Issue:
Description:
Measure:Phase II: Evaluation of tumor response based on duration of response as assessed by RECIST 1.1
Time Frame:From baseline (first dose) until disease progression or withdrawal from study, expected average 10 months
Safety Issue:
Description:
Measure:Phase II: Evaluation of tumor response based on tumor shrinkage as assessed by RECIST 1.1
Time Frame:From baseline (first dose) until disease progression or withdrawal from study, expected average 10 months
Safety Issue:
Description:
Measure:Phase II: Evaluation of tumor response based on progression free survival as assessed by RECIST 1.1
Time Frame:From baseline (first dose) until disease progression or withdrawal from study, expected average 10 months
Safety Issue:
Description:
Measure:Phase I: Change from baseline in QT/QTc interval
Time Frame:Cycle 1 Day 1 until disease progression or withdrawal from study, expected average 10 months
Safety Issue:
Description:
Measure:Phase I: Plasma concentrations of CK-101 following dosing with CK-101 as assessed by area under the curve
Time Frame:Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycle 2
Safety Issue:
Description:
Measure:Phase I: Plasma concentrations of CK-101 following dosing with CK-101 as assessed by maximum concentration
Time Frame:Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycle 2
Safety Issue:
Description:
Measure:Phase I: Plasma concentrations of CK-101 following dosing with CK-101 as assessed by elimination half-life
Time Frame:Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycle 2
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Checkpoint Therapeutics, Inc.

Trial Keywords

  • Cancer
  • Non Small Cell Lung Cancer
  • EGFR sensitivity mutation
  • T790M
  • NSCLC
  • epidermal growth factor receptor
  • EGFR
  • EGFR inhibitor

Last Updated

November 13, 2020