Phase 1/2 Study of LOXO-292 in Patients With Advanced Solid Tumours, RET Fusion-Positive Solid Tumours, and Medullary Thyroid Cancer

Official Title

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

Summary:

This is a Phase 1/2, open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumour activity of LOXO-292 administered orally to patients with advanced solid tumours, including RET-fusion-positive solid tumours, medullary thyroid cancer (MTC) and other tumours with RET activation.

Trial Description

Primary Outcome:

  • Phase 1: Maximum tolerated dose (MTD)
  • Phase 1: Recommended Phase 2 dose (RP2D)
  • Phase 2: Objective Response Rate
Secondary Outcome:
  • Phase 1: Frequency, severity, and relatedness of TEAEs and serious adverse events (SAEs), changes in hematology and blood chemistry values, assessments of physical examinations, vital signs, and electrocardiograms (ECGs).
  • Phase 1: Plasma concentration of LOXO-292 and PK parameters, including but not limited toarea under the curve from time 0 to 24 hours (AUC0-24), maximum drug concentration (Cmax), time to maximum plasma concentration (Tmax), and degree of accumulation.
  • Phase 1: ORR based on RECIST 1.1 or RANO, as appropriate to tumour type.
  • Phase 2: ORR (by Investigator)
  • Phase 2: best change in tumour size from baseline (by IRC and Investigator)
  • Phase 2: DOR (by IRC and Investigator)
  • Phase 2: CNS ORR (by IRC)
  • Phase 2: CNS DOR (by IRC)
  • Phase 2: time to any and best response (by IRC and Investigator)
  • Phase 2: CBR (by IRC and Investigator)
  • Phase 2: PFS (by IRC and Investigator)
  • Phase 2: OS
  • Phase 2: Frequency, severity and relatedness of TEAEs and SAEs, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and ECGs.
  • Phase 2: Plasma concentrations of LOXO-292 and PK parameters, including but not limited to AUC0-24, Cmax, and Tmax.
This is an open-label, multi-centre Phase 1/2 study in patients with advanced solid tumours, including RET fusion-positive solid tumours, MTC, and other tumours with RET activation. The trial will be conducted in 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). Patients with advanced cancer are eligible if they have progressed on or are intolerant to available standard therapies, or no standard or available curative therapy exists, or in the opinion of the Investigator, they would be unlikely to tolerate or derive significant clinical benefit from appropriate standard of care therapy, or they declined standard therapy. A dose of 160 mg BID has been selected as the recommended phase 2 dose (RP2D). Up to
  • 850 patients with advanced solid tumours harboring a RET gene alteration in tumour and/or blood will be enrolled to one of five phase 2 cohorts.
  • View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society