LYL273 for Patients With Relapsed or Refractory mCRC

Summary

This is a Phase 1/2 open-label, multicenter study evaluating the safety and efficacy of LYL273 in participants with relapsed or refractory metastatic colorectal cancer.

Detailed Description

LYL273-101 (CARABiNER) is a Phase 1/2 open label, multicenter study evaluating the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of LYL273, a GCC-targeted CAR T-cell product candidate enhanced with CD19 CAR expression and controlled cytokine release, in participants with relapsed or refractory metastatic colorectal cancer (mCRC). The study may enroll multiple dose expansion cohorts at the Sponsor's discretion to further characterize the safety, feasibility, and preliminary antitumor activity of LYL273 under defined treatment conditions including those defined below. 1. Cohorts to explore alternative mCRC patient populations Expansion cohorts may enroll a broader array of the mCRC population as listed below: * Earlier mCRC: Patients who have had a maximum of 1 prior line of systemic therapy 2. Cohorts to explore LYL273 in combination with other anti-cancer therapies Expansion cohorts may explore LYL273 in combination with consolidative radiotherapy. Up to 18 participants will be enrolled into each expansion cohort with up to approximately 95 patients enrolled in the Phase 1 portion of the study. The Phase 2 portion of the study will expand enrollment at the recommended Phase 2 dose of approximately 60 additional patients. LYL273 treatment consists of a single infusion of CAR-transduced autologous T cells administered intravenously after a conditioning chemotherapy regimen consisting of fludarabine and cyclophosphamide, administered once, 3 days before LYL273 infusion. Individual participants will remain in the active post-treatment follow-up (PTFU) period for up to 5 years. Participants will continue in long-term follow-up (LTFU) for 15 years from LYL273 treatment in a separate protocol.

Eligibility Criteria

Interventions