FDA Grants Fast Track Designation for Kymera’s KT-333 for the Treatment of Two Rare Cancers

Rare Daily Staff                                                   

The U.S. Food and Drug Administration has granted Fast Track designation to Kymera Therapeutics’ KT-333 for the treatment of R/R Cutaneous T-cell lymphoma and relapsed and/or refractory peripheral T-cell lymphoma.

The FDA’s Fast Track process is designed to get important new medicines to patients more quickly, facilitating the development and expediting the review of therapies intended to treat serious conditions and address unmet medical needs. Companies whose programs are granted Fast Track designation are eligible for more frequent interactions with the FDA during clinical development and potentially accelerated approval and/or priority review if relevant criteria are met.

Cutaneous T-cell lymphoma (CTCL) is a general term for non-Hodgkin’s T-cell lymphomas that are primarily characterized by an abnormal accumulation of T-cells in the skin and can involve the blood, lymph nodes and other internal organs. CTCL is a typically slow-growing cancer, with symptoms such as dry skin, potentially severe itching, rashes and enlarged lymph nodes. Since symptoms and skin biopsy findings are similar to other skin conditions, early-stage diagnosis can be difficult.

Peripheral T-cell lymphoma (PTCL), a subtype of non-Hodgkin’s lymphoma, is a heterogenous group of tumors that arise from mature T-cells in the lymphoid tissues in areas such as the lymph nodes, lungs, gastrointestinal tract and skin. PTCL carries a poorer prognosis than other non-Hodgkin’s lymphomas since it is less responsive to standard chemotherapy regimens.

KT-333 is a highly selective degrader of STAT3 in development for the treatment of multiple STAT3-dependent pathologies, including hematological malignancies and solid tumors. STAT3 is a transcriptional regulator that has been linked to numerous cancers as well as to inflammatory and autoimmune diseases. In 2022, KT-333 received FDA orphan drug designation for the treatment of both CTCL and PTCL.

“The KT-333 Fast Track designation highlights the promise of degrading STAT3, a protein that has historically been undruggable, for the treatment of patients with CTCL and PTCL,” said Jared Gollob, chief medical officer, Kymera Therapeutics. “We look forward to providing an update on the KT-333 phase 1 clinical trial later this year, including initial evaluation of its antitumor activity in the target patient populations, and to working with the lymphoma community to rapidly advance this first-in-class heterobifunctional degrader in CTCL and PTCL in addition to exploring its potential in other cancers.”

The phase 1 clinical trial of KT-333 is designed to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic and clinical activity of KT-333 dosed weekly in adult patients with relapsed and/or refractory lymphomas, leukemias and solid tumors. In June, Kymera presented data on thirteen patients who received a mean of five doses across the first four dose levels of the trial, including patients with solid tumors, CTCL and PTCL. With DL4 still open to accrual at the time of the presentation, data reported from DL1-3 found plasma exposure increased with dose, reaching levels close to those predicted to be efficacious, and demonstrated dose-dependent STAT3 degradation with up to 88% mean maximum reduction in peripheral blood mononuclear cells and degradation profiles at DL3 near levels of knockdown that led to antitumor activity in preclinical models. The phase 1a dose escalation stage is ongoing, recruiting broadly across solid and liquid tumors.

Photo: Jared Gollob, chief medical officer, Kymera Therapeutics