FDA Grants Orphan Drug Designation to Soquelitinib in T-Cell Lymphoma


Soquelitinib has been granted an orphan drug designation by the FDA for potential use in T-cell lymphoma.



The FDA has granted an orphan drug designation to soquelitinib (formerly CPI-818) as a potential therapeutic option for patients with T-cell lymphoma, according to an announcement by Corvus Pharmaceuticals, Inc.1

Soquelitinib is an oral, investigational small molecule drug designed to selectively inhibit interleukin-2-inducible T cell kinase (ITK), which is expressed in T cells and mediates both T cell and natural killer cell immune function.

Interim data from a phase 1/1b trial NCT03952078) presented at the 2022 ASH Annual Meeting demonstrated tumor responses with soquelitinib in patients with advanced, refractory T-cell lymphomas.2 Among the 11 patients with difficult-to-treat T-cell malignancies, 1 complete response (CR), 1 nodal CR, and 2 partial responses were achieved with a twice-daily 200 mg dose of soquelitinib, which was identified as the optimal dose. Soquelitinib was deemed well-tolerated at doses up to 600 mg twice a day, and no dose-limiting toxicities were observed.

Accordingly, initiation of a phase 3 clinical trial of the ITK inhibitor in relapsed peripheral T cell lymphoma (PTCL) is planned for the second quarter of 2024, as confirmed in a prior end-of-phase/pre-phase 3 meeting between the FDA and Corvus Pharmaceuticals, Inc.1,3

“Peripheral T cell lymphoma is an aggressive subset of non-Hodgkin’s lymphoma typically associated with a poor prognosis,” Richard A. Miller, MD, co-founder, president, and chief executive officer of Corvus, stated in a news release.1 “For these patients, there is significant need for new therapies given that existing drugs provide limited efficacy and are associated with significant toxicity.

Preclinical research on the mechanism of action of soquelitinib has indicated its potential for modulating normal T helper cell differentiation. By promoting the generation of cytotoxic killer T cells and cytokines that inhibit cancer cell survival, soquelitinib may bolster anti-tumor immune activity. Soquelitinib has also been shown to prevent T cell exhaustion, which is a current limitation of many immunotherapies and CAR T-cell therapies.1,4

At optimal doses, soquelitinib has induced the generation of Th1 helper cells, which promote tumor immunity, while inhibiting Th2 and Th17 cells, which are involved in autoimmune and allergic disease development.1

Furthermore, an analysis of the agent’s immune regulatory mechanism in the ongoing, international phase 1/1b trial was presented at the 2023 ASH Annual Meeting. Soquelitinib was found to induce normal CD4-positive Th1 cells and CD8-positive TEMRA cells and reduce CD4-positive T regulatory cells in the tumor micro-environment in responding patients.4

The analysis also showed that 3 of 8 evaluable patients experienced disease progression and 4 patients achieved stable disease. Common adverse effects (AEs) in less than 1% of patients included anemia, bilirubin increase, neutrophil count decrease, white blood cell decrease, and pruritus. Grade 3 or greater AEs were reported in 1 patient with neutrophil count decrease.

Based on this prior research, investigators feel that targeting specific molecular pathways in T cells with soquelitinib may benefit patients with cancers, particularly solid tumors.1

The planned phase 3 trial of soquelitinib aims to enroll 150 patients who have relapsed PTCL and have received no more than 3 prior therapies. Patients will be randomly assigned 1:1 to receive either soquelitinib at the optimal 200 mg dose or standard-of-care chemotherapy.3

The study’s primary end point will be progression-free survival. Key secondary end points will include objective response rate and overall survival.

There are no FDA-approved agents for relapsed PTCL,” Miller added in the news release. “The orphan drug designation is an important milestone in the development of soquelitinib that reinforces the unmet need for patients with T cell lymphoma.”


  1. Corvus Pharmaceuticals announces orphan drug designation granted to soquelitinib for the treatment of T cell lymphoma. News release. Corvus Pharmaceuticals. February 8, 2023. Accessed February 9, 2024. https://www.globenewswire.com/news-release/2024/02/08/2826449/0/en/Corvus-Pharmaceuticals-Announces-Orphan-Drug-Designation-Granted-to-Soquelitinib-for-the-Treatment-of-T-Cell-Lymphoma.html
  2. Song Y, Ding N, Yoon DH, et al. ITK inhibitor induces dose-dependent Th1 skewing in normal T cells and is active in refractory T cell lymphomas.Blood. 2022;140(suppl 1):8857-8859. doi:10.1182/blood-2022-159177
  3. Corvus Pharmaceuticals confirms planned initiation of soquelitinib (CPI-818) phase 3 registrational clinical trial in peripheral T cell lymphoma following meeting with FDA. News release. Corvus Pharmaceuticals, Inc. September 6, 2023. Accessed February 9, 2024. https://corvuspharma.gcs-web.com/news-releases/news-release-details/corvus-pharmaceuticals-confirms-planned-initiation-soquelitinib
  4. Ding N, Xie Yan, Guo Y, et al. Dynamic single-cell profiling reveals novel immune regulatory mechanism of ITK inhibitor soquelitinib in refractory T cell lymphoma. Blood. 2023;142(suppl 1):1442. doi:10.1182/blood-2023-174421

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