Timeframe: 2025 – 2028
Goal: Provide the drug necessary to enable a FLC clinical trial
Grantee: Dialectic Therapeutics, Inc.
Principal Investigators of related clinical study: Dr. Allison O’Neill, Dana-Farber Cancer Institute and Dr. Michael Ortiz, Memorial Sloan Kettering Cancer Center
Effort overview: This grant funds the manufacturing and distribution of an experimental drug, DT2216, for a clinical trial for fibrolamellar patients. The Foundation’s funding of the manufacturing costs of the drug was essential to ensure that the fibrolamellar-specific clinical trial could be launched.
Dialectic Therapeutics, Inc. is a Texas-based clinical stage biotechnology company focused on creating innovative new technologies to treat cancer. DT2216 is their first-in-class anticancer agent that targets a protein called BCL-XL, the most commonly over-expressed anti-apoptotic protein in cancer. Anti-apoptotic proteins help prevent programmed cell death (apoptosis) in cells, allowing them to survive longer than they normally would. They play a crucial role in cell survival and cancer development. By degrading BCL-XL, DT2216 can stimulate cancer cells to commit suicide or become more susceptible to chemotherapy.Â
The supported clinical trial, sponsored by the Children’s Oncology Group (COG) and led by Dr. Michael Ortiz of the Memorial Sloan Kettering Cancer Center and Dr. Allison O’Neill from the Dana-Farber Cancer Institute, is open at major medical centers throughout the U.S. This phase 1/2 study, 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, tests the safety, side effects and best dose of DT2216 in combination with the chemotherapy agent, irinotecan. This study’s availability in a broad network of pediatric institutions should allow many FLC patients to join the trial at medical centers within reasonable distances from their homes.
This clinical effort is based on research conducted by Sanford Simon, PhD of Rockefeller University several years ago. The Rockefeller team observed that cancer cells from certain FLC patients could be killed by some chemotherapy drugs, including irinotecan. However, that susceptibility to the chemotherapy treatment correlated inversely with the FLC cells’ expression of BCL-XL. Fibrolamellar cells with low levels of BCL-XL were killed, while higher amounts of BCL-XL appeared to protect the cancer cells from the chemotherapy. Additional preclinical studies confirmed that the combination of DT2216 and irinotecan can synergize and shrink human FLC tumors with elevated levels of BCL-XL.
More information about the trial and its locations is available at clinicaltrials.gov/study/NCT06620302.