Phase 1/2 Study of LOXO-292 in Participants 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)


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 selpercatinib (also known as LOXO-292) administered orally to participants with advanced solid tumours, including rearranged during transfection (RET)-fusion-positive solid tumours, medullary thyroid cancer (MTC) and other tumours with RET activation.

Trial Description

Primary Outcome:

  • Phase 1: MTD
  • Phase 1: RP2D
  • Phase 2: Objective Response Rate
Secondary Outcome:
  • Phase 1: Number of Participants with a Treatment-Related Adverse Event(s) (TRAE[s])
  • Phase 1: Number of Participants with an Abnormal Laboratory or Physical Exam Result(s)
  • Phase 1: Overall Response Rate (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: Duration of Response (DOR; by IRC and Investigator)
  • Phase 2: Central Nervous System (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: Overall Survival (OS)
  • Phase 2: Percentage of Participants with any Serious Adverse Event (SAE[s])
  • Phase 1 and 2: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve of LOXO-292 (Selpercatinib)
  • Phase 1 and 2: PK: Maximum Concentration (Cmax) of LOXO-292 (Selpercatinib)
This is an open-label, multi-centre Phase 1/2 study in participants 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). Participants 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 milligrams (mg) twice a day (BID) has been selected as the recommended phase 2 dose (RP2D). Up to approximately 950 participants with advanced solid tumours harboring a RET gene alteration in tumour and/or blood will be enrolled to one of six phase 2 cohorts. Cohort 7 has been included as a US-only protocol addendum, which plans to enroll approximately 19 eligible, RET fusion-positive, early stage NSCLC participants, to receive selpercatinib in a neoadjuvant and adjuvant setting. Participants will be followed for disease recurrence for a total of 5 years from the date of surgery.

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Canadian Cancer Society

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