MC# 20-16 - An Open-Label, Multicenter, Phase IB/II Study to Establish Safety, Tolerability, and Optimal Dosing Strategy of GLR2007 in Subjects with Advanced Solid Tumors

  • Agent(s): GLR2007
  • Disease Type(s): Solid Tumor, Lung-NSCLC, Glioblastoma, Brain metastases of breast or NSCLC origin
  • Phase(s): I, II
  • Drug Classification(s): Targeted Therapy, Small Molecule
  • Molecular Target(s): CDK4/6

Mechanism of Action

GLR2007 is a CDK4/6 inhibitor, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth.

Purpose

In this study, the sponsor and investigators want to learn:

  • About the safety and tolerability of GLR2007
  • How proteins that indicate the status of your disease are affected with use of GLR2007
  • If GLR2007 prevents or delays tumor growth or shrinks existing tumors
  • How much of GLR2007 is absorbed into the blood and how fast it is removed
  • If research tests can be used in the future to predict who will benefit from GLR2007
Inclusion Criteria
  1. The subject is ≥18 years of age.
  2. For Part 1 (Dose Escalation): Subjects with advanced solid tumors who are refractory or intolerant to therapies known to provide clinical benefit
    1. For Part 1 (Dose Escalation): The subject must have histological or cytological evidence of cancer (a solid tumor) that is advanced and/or metastatic.  Biopsy is allowed by protocol if no histology or cytology records are available.
    2. For Part 2 (Dose Expansion): The subject must have histological or cytological evidence of 1 of the following cancers that is advanced and/or metastatic:
      1. Cohort A: ≥2L NSCLC
      2. Cohort B: ≥2L Brain metastases of breast or NSCLC origin
      3. Cohort C: First recurrence GBM
  3. For Part 1 (Dose Escalation): The subject has measurable or non-measurable disease
  4. For Part 2 (Dose Expansion): The subject has measurable disease
  5. The subject has given written informed consent prior to all study-specific procedures
  6. The subject has adequate hematologic, hepatic, and renal function as demonstrated by:
    1. Absolute neutrophil count (ANC) ≥1,000/µL
    2. Platelet count ≥75,000/µL
    3. Hemoglobin ≥8 g/dL (subjects may be transfused to this level if necessary)
    4. Aspartate transaminase (AST) and alanine transaminase (ALT) values ≤2.5× the upper limit of normal (ULN) (≤5× ULN if the liver is known to be involved by metastatic disease) and serum total bilirubin values of ≤1.5× ULN (≤2× ULN for subjects with known Gilbert’s syndrome) for the reference laboratory
    5. Serum creatinine ≤1.5× ULN for the reference laboratory or a calculated creatinine clearance (CL) of ≥60 mL/min by the Cockcroft-Gault equation
  7. The subject is ambulatory with an Eastern Cooperative Oncology Group performance status of 0, 1, or 2
  8. The subject has discontinued all prior cancer therapies (including chemotherapy and investigational therapy) for at least 21 days for myelosuppressive agents or 14 days for radiotherapy and non-myelosuppressive agents, or 28 days for immunotherapies prior to receiving the first dose of GLR2007, and has recovered from the acute effects of therapy (treatment-related toxicity resolved to ≤Grade 1) except for residual alopecia
  9. The subject is willing and able to make themselves available for the duration of the study and is willing and able to follow study procedures
  10. The subject meets contraceptive requirements.  Female subjects must agree to use 2 highly reliable methods of birth control from the Screening Visit through 28 days after the last dose of GLR2007.  All women of childbearing potential must have 2 negative pregnancy tests prior to initiating therapy, one 30 days before initiating GLR2007 and one the day prior to initiating GLR2007.  Women <50 years old with amenorrhea for <2 years and who have not had a hysterectomy and oophorectomy will only be considered not to be of reproductive potential if they have a documented follicle-stimulating hormone value in the postmenopausal range.
  11. The subject has an estimated life expectancy of ≥3 months
  12. The subject agrees to minimize UV exposure and sunlight for the duration of their study participation
  13. A diagnostic contrast-enhanced MRI of the brain must be performed within 28 days prior to registration.  Contrast-enhanced CT is acceptable if MRI is not possible.
Exclusion Criteria
  1. The subject has a personal history of any of the following conditions: major surgical resection involving the stomach or small bowel recurrent, unexplained or cardiac-related syncopal episodes within the last 6 months or ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation)
  2. Any concurrent malignancies currently requiring treatment or for which treatment would be deemed necessary within 3 months of enrollment; prostate cancer with androgen deprivation therapy, basal cell cancer, and squamous cell cancers are allowed
  3. Any serious or uncontrolled health condition that, in the opinion of the investigator, medical monitor, or sponsor, would place the subject at undue risk from the study, impair the ability of the subject to receive protocol-specified therapy, or interfere with the interpretation of study results (eg, <6 months prior to the first dose of GLR2007: clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, viral myocarditis, cerebrovascular accident, left ventricular ejection fraction <50%, New York Heart Association Class III or IV congestive heart failure, or uncontrolled hypertension [systolic BP >150 mmHg or diastolic BP >100 mmHg] at screening, despite optimal antihypertensive therapy, or other acute uncontrolled heart disease; hemodynamically significant pulmonary embolism requiring hospitalization; or active interstitial lung disease or pneumonitis or a history thereof requiring treatment with steroids or other immunosuppressive medications <3 months)
  4. The subject is pregnant or lactating
  5. The subject is immunocompromised and known to be human immunodeficiency virus positive.  The subject has an active bacterial, fungal, and/or known viral infection (eg, hepatitis B surface antigen or hepatitis C antibodies).
  6. The subject is unable to swallow the capsule or has refractory nausea and vomiting, malabsorption, external biliary diversion, or any significant small bowel resection that may interfere with adequate absorption of Investigational Product (IP)
  7. The subject is taking medications that are strong CYP3A inhibitors (eg, clarithromycin, itraconazole) or strong CYP3A inducers (eg, phenytoin, rifampicin); strong CYP3A inhibitors or inducers should be discontinued at least 14 days prior to the first dose of GLR2007
  8. Triplicate average QTc, QTcB, or QTcF>450 msec; or QTc >480 msec in subjects with bundle branch block
  9. The subject is taking medications that prolong the QT/QTc interval
  10. A history of additional risk factors for Torsade de Pointes (eg, heart failure, hypokalemia, family history of Long QT Syndrome)

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://www.clinicaltrials.gov/ct2/show/NCT04444427

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Re: MC# 20-16