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Protocol No. UW18059

Principal Investigator Burkard, Mark

Phase I

Age Group Adult

Scope National

Sponsor Type Industry

Title A Phase 1/2 Study of Oral LOXO-292 in Patients with Advanced Solid Tumors, Including RET Fusion-Positive Solid Tumors, Medullary Thyroid Cancer, and Other Tumors with RET Activation (LIBRETTO-001)

This research study is being done to determine the safety of an investigational treatment called LOXO-292. LOXO-292 is an oral investigational drug that may treat cancer. Neither the FDA (U.S. Food and Drug Administration) nor any other health or regulatory authority in other countries have approved LOXO-292. This study will be the first time LOXO-292 will be taken by humans. The main purposes of this research study include the following:
  • To determine whether LOXO-292 is safe;
  • To identify which dose level of LOXO-292 should be studied in future studies;
  • 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 LOXO-292;
  • To evaluate how the body absorbs and processes different doses of LOXO-292 by measuring the levels of LOXO-292 in the blood at different times (this is called pharmacokinetic (PK) testing);
  • To determine how well your cancer responds to LOXO-292;
  • To determine how long any benefits from treatment with LOXO-292 last.

  • Treatment
    This study will be conducted in two parts: dose escalation and dose expansion
    During dose escalation, LOXO-292 will be studied at 8 or more different total daily dose levels in groups or cohorts (where each different group may be assigned to a higher dose). 3 to 6 patients will be enrolled in each dose group. Once a group has completed dosing and safety has been assessed, the next group will be enrolled

    Description Phase I LOXO-292 in advanced solid tumors(RET-Fusion Non-Small Cell Lung Cancer, Medullary thyroid and other tumors with RET activity)

    Key Eligibility
  • Patients with a locally advanced or metastatic solid tumor that: has progressed following standard therapy, or has not adequately responded to standard therapy, or for which no standard therapy exists, or patients who decline standard therapy, or In the opinion of the Investigator, are not candidates for, or would be unlikely to tolerate or derive significant clinical benefit from standard therapy
  • Any number of prior TKIs with anti-RET activity are allowed
  • Evidence of a RET gene alteration in tumor and/or blood (e.g., gene rearrangement and/or mutation,excluding synonymous, frameshift or nonsense mutations), as identified through molecular assays, as performed for clinical evaluation
  • Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
  • At least 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Archived tumor tissue sample available
  • Adequate hematologic, hepatic and renal function
  • Ability to swallow capsules and comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
  • Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following the last dose of study treatment
  • For NSCLC patients, an additional known oncogenic driver. Examples include targetable mutation in EGFR, targetable rearrangement involving ALK or ROS1, or KRAS (dose expansion only). Such patients may be enrolled to Cohort 5 with prior Sponsor approval
  • Major surgery (excluding placement of vascular access) within 4 weeks prior to planned start of LOXO-292
  • Symptomatic primary central nervous system (CNS) tumor or metastases; symptomatic leptomeningeal carcinomatosis; untreated spinal cord compression
  • Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months
  • Active uncontrolled systemic bacterial, viral, or fungal infection
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug
  • Uncontrolled symptomatic hyperthyroidism or hypothyroidism
  • Uncontrolled symptomatic hypercalcemia or hypocalcemia
  • Current treatment with proton pump inhibitors (PPIs)
  • Active second malignancy other than minor treatment of indolent cancers
  • Pregnant or breastfeeding

  • Applicable Disease Sites Lung; Thyroid; Unknown Sites

    Status Open

    Participating Institutions UW Hospital and Clinics