NCT06620302

Testing the Addition of an Anti-cancer Drug, DT2216, to the Usual Chemotherapy Treatment for Relapsed or Refractory Solid Tumors and Fibrolamellar Carcinoma

Recruiting now Phase 1, PHASE2 Last updated 24 February 2026

What this trial tests

Phase 1, PHASE2 trial testing Bcl-XL Proteolysis Targeting Chimera DT2216 in Childhood Fibrolamellar Carcinoma in 81 participants. Currently enrolling.

Timeline

12 June 2025

Primary endpoint
30 December 2031

30 December 2031

Quick facts

Lead sponsor	Children's Oncology Group
Phase	Phase 1, PHASE2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	81
Start date	12 June 2025
Primary completion	30 December 2031
Estimated completion	30 December 2031
Sites	20 locations across United States

Drugs / interventions tested

• Bcl-XL Proteolysis Targeting Chimera DT2216 — full drug profile →
• Biospecimen Collection — full drug profile →
• Irinotecan (irinotecan) — full drug profile →

Conditions studied

• Childhood Fibrolamellar Carcinoma — all drugs for Childhood Fibrolamellar Carcinoma →
• Recurrent Childhood Fibrolamellar Carcinoma — all drugs for Recurrent Childhood Fibrolamellar Carcinoma →
• Recurrent Childhood Malignant Solid Neoplasm — all drugs for Recurrent Childhood Malignant Solid Neoplasm →
• Recurrent Fibrolamellar Carcinoma — all drugs for Recurrent Fibrolamellar Carcinoma →

Sponsor

Children's Oncology Group — full company profile →

Who can join

Adults 1 to 39, any sex, with Childhood Fibrolamellar Carcinoma or Recurrent Childhood Fibrolamellar Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This phase I/II trial tests the safety, side effects and best dose of DT2216 in combination with irinotecan and how well it works in treating children, adolescents and young adults with solid tumors and fibrolamellar cancer that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). DT2216 is an anti-apoptotic protein B-cell lymphoma-extra large targeted protein degrader. It may stop the growth of tumor cells by blocking Bcl-xL, a protein needed for tumor cell survival. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid repair and may kill tumor cells. Giving DT2216 in combination with irinotecan may be safe, tolerable, and/or effective in treating children, adolescents and young adults with relapsed or refractory solid tumors or fibrolamellar cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeted protein degradation: advances in drug discovery and clinical practice.
   Zhong G, Chang X, Xie W, Zhou X. · · 2024 · cited 112× · PMID 39500878 · DOI 10.1038/s41392-024-02004-x
2. NDA Submission of Vepdegestrant (ARV-471) to U.S. FDA: The Beginning of a New Era of PROTAC Degraders.
   Ma Z, Zhou J. · · 2025 · cited 28× · PMID 40702893 · DOI 10.1021/acs.jmedchem.5c01818
3. First in human phase 1 study of DT2216, a selective BCL-xL degrader, in patients with relapsed/refractory solid malignancies.
   Mahadevan D, Barve M, Mahalingam D, Parekh J, et al · · 2025 · cited 8× · PMID 41225624 · DOI 10.1186/s13045-025-01753-8
4. Proteolysis-Targeting Chimera (PROTAC): Current Applications and Future Directions.
   Fan G, Chen S, Zhang Q, Yu N, et al · · 2025 · cited 6× · PMID 41049269 · DOI 10.1002/mco2.70401
5. Targeted protein degradation with small molecules for cancer immunotherapy.
   Yang Z, Xu J, Yang X, Chen J. · · 2025 · cited 3× · PMID 40791660 · DOI 10.1016/j.ajps.2025.101058
6. Discovery of PZ671, a highly potent and <i>in vivo</i> active CRBN-recruiting Bcl-xL degrader.
   Zhang P, Thummuri D, Hu W, Khan S, et al · · 2025 · cited 2× · PMID 40510905 · DOI 10.1039/d5md00119f
7. E3 Ubiquitin Ligases: Structures, Biological Functions, Diseases, and Therapy.
   Wang H, Peng J, Li H, Lan Y, et al · · 2025 · cited 1× · PMID 41362701 · DOI 10.1002/mco2.70528
8. Unraveling the meta-hallmarks between senescent and tumor cells: A new perspective for senolytic drug discovery.
   Liu W, Fan B, Fang T, Li H, et al · · 2025 · cited 1× · PMID 41132829 · DOI 10.1016/j.apsb.2025.08.010