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

A Phase I/II, Open-Label, Safety, Pharmacokinetic and Efficacy Study of Ascending Doses of Oral CK-101 in Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Lung Diseases; Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms
• Intervention / Treatment: Drug: CK-101

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.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Research Site
• New Zealand
  • Christchurch, New Zealand, 8011
    • Research Site
  • Wellington, New Zealand, 6021
    • Research Site
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Research Site
• Poland
  • Kujawsko-Pomorskie
    • Bydgoszcz, Kujawsko-Pomorskie, Poland, 85-231
      • Research Site
    • Bydgoszcz, Kujawsko-Pomorskie, Poland, 85-796
      • Research Site
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-064
      • Research Site
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-044
      • Research Site
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 60-693
      • Research Site
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 70-784
      • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Research Site, Pathumwan
  • Bangkok, Thailand, 10400
    • Research Site, Ratchathewi District
  • Bangkok, Thailand, 10700
    • Research Site, Bangkok Noi District
  • Chiang Mai, Thailand, 50200
    • Research Site, Muang District
  • Khon Kaen, Thailand, 40002
    • Research Site
  • Phitsanulok, Thailand, 65000
    • Research Site, Muang
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site

Participation Criteria

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daily dose of CK-101; Daily oral dose of CK-101	Drug: CK-101; Phase 1: CK-101 will be administered in escalating dosages in a period of 21-day cycles Phase 2: CK-101 will be administered daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase I: Incidence of dose-limiting toxicities (DLTs)	From baseline (first dose) to 28 days after last dose, expected average 6 months
Phase II: Objective response rate (ORR): Defined as the rate of complete responses [CR] or partial responses [PR] per RECIST Version 1.1 as assessed by an independent central review	From baseline (first dose) until disease progression or withdrawal from study, expected average 10 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Checkpoint Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: September 29, 2016
• First Submitted That Met QC Criteria: October 5, 2016
• First Posted (Estimate): October 6, 2016

Study Record Updates

• Last Update Posted (Actual): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Cancer; NSCLC; Non Small Cell Lung Cancer; EGFR; EGFR inhibitor; T790M; epidermal growth factor receptor; EGFR sensitivity mutation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Diseases; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: CK-101-101