Folotyn (pralatrexate)

P3, N=218, Recruiting, Dizal Pharmaceuticals

P1/2, N=50, Not yet recruiting, Fred Hutchinson Cancer Center

P2, N=20, Not yet recruiting, The FIrst Affiliated Hospital, College of Medicine, Zhejiang University; The FIrst Affiliated Hospital, College of Medicine, Zhejiang University

P1, N=37, Active, not recruiting, University of Virginia | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> May 2026

Inhibition of one-carbon metabolism at a different node, using the clinically relevant dihydrofolate reductase inhibitor Pralatrexate, similarly yields a profound growth inhibition, with depletion of thymidylate and purine nucleotides. Genetic depletion of SHMT2 dramatically impairs tumor growth in a xenograft model of EWS. Together, these data establish dependence on one-carbon metabolism as a novel and targetable vulnerability of EWS cells, which can be exploited for therapy.

P2, N=50, Recruiting, University of Virginia | Trial completion date: Jun 2028 --> Jun 2030 | Trial primary completion date: Jun 2026 --> Jun 2028

There were no pathological or immunohistochemical findings common to cases that responded to pralatrexate, however, of the four PTCL-NOS patients, two were GATA3 positive. Although there are limitations due to the number of cases, considering that the response rate of pralatrexate for PTCL-NOS in existing studies was 32%, these results may lead to future advances in PTCL treatment.

P1/2, N=13, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2025 --> Feb 2026

P1, N=24, Recruiting, Acrotech Biopharma Inc.

At a median follow-up of 45 months, 6 (33%) patients remain in sustained remission. This retrospective analysis is the first to evaluate pralatrexate's efficacy in this aggressive disease population, demonstrating its effectiveness and association with durable responses in cytotoxic CTCL.

Inhibition of one-carbon metabolism at a different node, using the clinically relevant dihydrofolate reductase inhibitor Pralatrexate, similarly yields a profound growth inhibition, with depletion of thymidylate and purine nucleotides...Together, these data establish the upregulation of the one-carbon metabolism as a novel and targetable vulnerability of EWS cells, which can be exploited for therapy. Using both genetic and pharmacologic approaches, this study identifies Ewing sarcoma's dependence on the mitochondrial arm, but not the cytoplasmic arm, of one-carbon metabolism as a targetable vulnerability that can be effectively harnessed for therapy.

P3, N=150, Recruiting, Corvus Pharmaceuticals, Inc. | Trial completion date: Sep 2027 --> Jul 2028 | Trial primary completion date: Feb 2026 --> Nov 2026