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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: CK-101


Participation Criteria
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Eligibility Criteria
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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: 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 Metastatic or unresectable locally advanced NSCLC: 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 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daily dose of CK-101<br>Daily oral dose of CK-101 | Drug: CK-101<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Non Small Cell Lung Cancer, EGFR sensitivity mutation, T790M, NSCLC, epidermal growth factor receptor, EGFR, EGFR inhibitor