Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

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

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 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: Inclusion Criteria:
  -  Diagnosis with a histologically confirmed non-small cell lung cancer (NSCLC) or other refractory solid tumor that is metastatic or unresectable for which there is no standard curative or palliative treatment option available and where targeting EGFR may be appropriate
  -  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
  -  Phase 2 patients must have confirmed EGFR T790M mutation-positive NSCLC
  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
  -  Phase 2 patients are also excluded if they had prior treatment with CK-101 or other third generation TKIs that target EGFR T790M mutation-positive NSCLC, or have evidence that the tumor harbors an exon 20 insertion mutation

Relevance to patient case: definitely relevant