DT2216 in Combination With Irinotecan

Trial snapshot

  • Formal name: DT2216 in Combination With Irinotecan for Children, Adolescents and Young Adults With Relapsed or Refractory Solid Tumors: A Phase I Study With Phase II Feasibility Cohort for Fibrolamellar Carcinoma
  • Trial type: Specifically designed for fibrolamellar carcinoma
  • Phase: Phase I
  • Recruitment status: Active, Not recruiting
  • Eligible ages: <19
  • Locations: 21 sites within the Pediatric Early Phase‑Clinical Trial Network (PEP‑CTN)
  • ClinicalTrials.gov reference: NCT06620302

Overview

This phase I/II clinical trial will evaluate the safety, side effects, and optimal dosage of DT2216 combined with irinotecan, as well as its effectiveness in treating children, adolescents, and young adults with relapsed (returned after improvement) or refractory (non-responsive to prior treatment) FLC. DT2216 is a targeted protein degrader that inhibits BCL-XL, an anti-apoptotic protein essential for tumor cell survival, potentially stopping tumor growth. Irinotecan, a topoisomerase I inhibitor, disrupts cell division and DNA repair, which may lead to tumor cell death.

The clinical trial is based on research led by Sandy Simon, PhD of Rockefeller University that showed that FLC cells are sensitive to irinotecan, but that sensitivity is inversely correlated with the cells’ expression of BCL-XL.

DT2216 is an investigational drug developed by Dialectic Therapeutics that avoids a complication found with conventional BCL-XL inhibitors – impaired blood clotting caused by a drop in the number of platelets, which are rich in BCL-XL. Dialectic Therapeutics has previously completed a Phase 1 first-in-human study of DT2216 in patients with various cancers. This trial established DT2216’s safety and tolerability, and it confirmed that the drug does not cause thrombocytopenia (low platelet count). The initial trial also established a phase 2 dose for the single agent, and it laid solid groundwork for this study of DT2216 in combination with irinotecan.

Trial eligibility

The initial Phase 1 portion of this study will be carried out in patients between ages 1 and 21 years with recurrent and/or treatment-refractory solid tumors. This phase will include FLC patients; however, many subjects may have other cancers. The Phase 2 portion of the study will be carried out exclusively in FLC patients up to 39 years old.

Trial details

The main goal of the Phase 1 portion of the trial will be to determine a recommended Phase 2 dose of DT2216, administered in combination with a standard dose of irinotecan. The study also will assess the pharmacokinetics of DT2216 (how the drug is absorbed, distributed, chemically altered, and excreted by the body), and its toxicities. This component of the study will assess, to the extent possible, the anti-tumor activity of DT2216 in combination with irinotecan in patients with solid tumors, including any patients with FLC. Between 6 and 24 evaluable patients will be required to complete the dose escalation portion of the study.

During the Phase 2 portion of the study, DT2216 will be administered at the recommended dose established in Phase 1, together with irinotecan at its standard dose. Its main goal will be to define anti-tumor activity of the DT2216/irinotecan combination in FLC patients. Between 8 and 15 patients will be enrolled in this phase.

More information about the study can be read here: https://clinicaltrials.gov/study/NCT06620302.

Trial contact information:

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