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

Checkpoint Therapeutics

Status and phase

Completed

Phase 1

Conditions

Lung Neoplasms

Lung Diseases

Carcinoma, Non-Small-Cell Lung

Adenocarcinoma

Treatments

Drug: CK-101

Study type

Interventional

Funder types

Industry

Identifiers

NCT02926768

CK-101-101

Details and patient eligibility

About

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.

Full 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.

Enrollment

136 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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