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Protocol No. UW19004

Principal Investigator Burkard, Mark

Phase I/II

Age Group Adult

Scope National

Sponsor Type Industry

Title Phase 1 / 2 Multicenter Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of APL-101 in Subjects with Non-Small Cell Lung Cancer with c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors

Objective This research study is being done to determine the safety of an investigational treatment called APL-101. APL-101 is an investigational drug that inhibits the protein c-Met. It is taken as a pill twice a day on an empty stomach. Treatments targeting c-Met, including APL-101, have been shown to work in mice and are being tested in multiple cancer types in humans. None of these treatments have been approved by the FDA to date The main purposes of this research study include the following: To determine whether APL-101 is safe, to identify which of the dose levels used in this study is the highest tolerated dose or the dose that causes side effects that are too severe to continue treatment with APL-101, to identify which dose of APL-101 should be studied in future studies, to determine how well your cancer responds to APL-101, to evaluate how the body absorbs and processes different doses of APL-101 by measuring the levels of APL-101 in the blood at different times (this is called pharmacokinetic (PK) testing); to evaluate how certain protein levels in your body change after taking APL-101 by measuring them in your blood at different times (this is called pharmacodynamics (PD) testing; and to determine how long any benefits from treatment with APL-101 last

Treatment This study has two parts: Phase 1 (Dose Escalation) and Phase 2 (Dose and Disease Expansion). Whether you enter the Dose Escalation part or the Dose and Disease Expansion part depends on when you enter the study. In either part, APL-101 will be given to you to be taken orally

Description Phase 1/2 Study of APL-101 in Subjects with Non-Small Cell Lung Cancer with c-Met EXON 14 and c-Met Dysregulation Tumors

Key Eligibility
  • Men and women 18 years of age or older
  • For Phase 1, histologically and / or cytological confirmed locally advanced, recurrent or relapsed or metastatic incurable solid malignancy with no limit on the number of prior lines of standard therapy or for whom no standard therapy exist
  • For Phase 2, three cohorts will be enrolled: Cohort A: EXON 14 NSCLC (c-Met na├»ve), Cohort B: EXON 14 NSCLC (c-Met experienced; progressed on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met dysregulation (amplification or mutation or fusions) as defined by the protocol
  • Measurable disease according to RECIST v1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0–1
  • Acceptable organ function as defined by the protocol
  • No chemotherapy treatments within at least 3 weeks prior to first dose of study treatment. For all prior anticancer treatment, including radiotherapy or targeted agents or hormonal therapy, a duration of more than 5 half-lives of the targeted/hormonal agents used must have elapsed, and any encountered toxicity must have resolved to levels meeting all the other eligibility criteria
  • Adequate cardiac function (less than or equal to NYHA class II) or normal cardiac function with left ventricular ejection fraction (LVEF) greater than or equal to 50% at screening
  • Woman and men of child bearing potential must agree to adequate birth control as defined but the protocol
  • Can not be pregnant or breast feeding
  • Must be able to swallow pills
  • Known mutation of EGFR, ALK or ROS1 or have received a kinase inhibitor for these mutations
  • Poor medical risk because of systemic diseases (e.g., active uncontrolled infections) in addition to the advanced malignancy under study
  • History of, or at risk for, cardiac disease (e.g., long QT syndrome [greater than 450 msec] or concurrent treatment with any medication that prolongs QT interval)
  • Known history of human immunodeficiency virus (HIV), or historical seropositive results consistent with active infection for hepatitis C virus (HCV) or hepatitis B virus (HBV) with high viral loads not actively managed with antiviral therapy. If history is unclear, a test at Screening will be required
  • Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptic and requiring high doses of steroids (greater than 10 mg/day of prednisone or equivalent)
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., Crohn’s, ulcerative colitis, active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome)

  • Applicable Disease Sites Anal; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Hematologic cancers, other; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

    Status Open

    Participating Institutions UW Hospital and Clinics