Clinical trial NCT02926768: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Diseases
Adenocarcinoma
Keywords: Cancer
Non Small Cell Lung Cancer
EGFR sensitivity mutation
T790M
NSCLC
epidermal growth factor receptor
EGFR
EGFR inhibitor
Lead sponsor: Checkpoint Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-10-06
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Phase I: Incidence of dose-limiting toxicities (DLTs)
timeFrame: From baseline (first dose) to 28 days after last dose, expected average 6 months
measure: 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
timeFrame: From baseline (first dose) until disease progression or withdrawal from study, expected average 10 months
Secondary outcomes:
measure: Phase II: Evaluation of tumor response based on disease control rate as assessed by RECIST 1.1
timeFrame: From baseline (first dose) until disease progression or withdrawal from study, expected average 10 months
measure: Phase II: Evaluation of tumor response based on duration of response as assessed by RECIST 1.1
timeFrame: From baseline (first dose) until disease progression or withdrawal from study, expected average 10 months
measure: Phase II: Evaluation of tumor response based on tumor shrinkage as assessed by RECIST 1.1
timeFrame: From baseline (first dose) until disease progression or withdrawal from study, expected average 10 months
measure: Phase II: Evaluation of tumor response based on progression free survival as assessed by RECIST 1.1
timeFrame: From baseline (first dose) until disease progression or withdrawal from study, expected average 10 months
measure: Phase I: Change from baseline in QT/QTc interval
timeFrame: Cycle 1 Day 1 until disease progression or withdrawal from study, expected average 10 months
measure: Phase I: Plasma concentrations of CK-101 following dosing with CK-101 as assessed by area under the curve
timeFrame: Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycle 2
measure: Phase I: Plasma concentrations of CK-101 following dosing with CK-101 as assessed by maximum concentration
timeFrame: Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycle 2
measure: Phase I: Plasma concentrations of CK-101 following dosing with CK-101 as assessed by elimination half-life
timeFrame: Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycle 2
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Research Site
state: Florida
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Greenslopes
country: Australia
facility: Research Site
state: Queensland
city: Grafton
country: New Zealand
facility: Research Site
state: Auckland
city: Christchurch
country: New Zealand
facility: Research Site
city: Wellington
country: New Zealand
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
state: Kujawsko-Pomorskie
city: Bydgoszcz
country: Poland
facility: Research Site
state: Kujawsko-Pomorskie
city: Lublin
country: Poland
facility: Research Site
state: Lubelskie
city: Białystok
country: Poland
facility: Research Site
state: Podlaskie
city: Poznań
country: Poland
facility: Research Site
state: Wielkopolskie
city: Szczecin
country: Poland
facility: Research Site
state: Zachodniopomorskie
city: Bangkok
country: Thailand
facility: Research Site, Pathumwan
city: Bangkok
country: Thailand
facility: Research Site, Ratchathewi District
city: Bangkok
country: Thailand
facility: Research Site, Bangkok Noi District
city: Chiang Mai
country: Thailand
facility: Research Site, Muang District
city: Khon Kaen
country: Thailand
facility: Research Site
city: Phitsanulok
country: Thailand
facility: Research Site, Muang
Study officials:
References: