A Study of LOXO-292 in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)

A Study of LOXO-292 in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)

Brief Summary:
This is an open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib (also known as LOXO-292) administered orally to participants with advanced solid tumors, including rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation.

Detailed Description:
This is an open-label, multi-center Phase 1/2 study in participants with advanced solid tumors, including RET fusion-positive solid tumors, MTC, and other tumors with RET activation. The trial will be conducted in 2 parts: Phase 1 (dose escalation - completed) 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). Approximately 950 participants with advanced solid tumors harboring a RET gene alteration in tumor and/or blood will be enrolled to one of seven phase 2 cohorts:
- Cohort 1: Advanced RET fusion positive solid tumor for participants who progressed on or intolerant to first line therapy (open)
- Cohort 2: Advanced RET fusion positive solid tumor for treatment naïve participants (open)
- Cohort 3: Advanced RET-mutant MTC participants who progressed on or intolerant to first line therapy (closed)
- Cohort 4: Advanced RET-mutant MTC participants who are treatment naïve (closed)
- Cohort 5: Advanced RET-altered solid tumor for participants otherwise ineligible for cohorts 1-4. See details in inclusion/exclusion criteria (open)
- Cohort 6: Participants otherwise eligible for Cohorts 1-5 who discontinued another RET inhibitor due to intolerance may be eligible with prior Sponsor approval (open)
- Cohort 7: RET fusion positive early-stage non-small cell lung cancer (NSCLC) participants who are candidates for definitive surgery. Participants will receive selpercatinib in a neoadjuvant and adjuvant setting. Participants will be followed for disease recurrence for up to 5 years from the date of surgery (open in US only)


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 989 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 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)
Actual Study Start Date: May 2, 2017
Estimated Primary Completion Date: November 21, 2022
Estimated Study Completion Date: November 21, 2023

Arm:
- Experimental: LOXO-292

View full details