Soquelitinib Receives FDA Orphan Drug Designation for T-Cell Lymphomas

• Soquelitinib (formerly known as CPI-818) is an interleukin-2-inducible T cell kinase (ITK) inhibitor that has shown promise in treating patients with T-cell lymphomas.

• A phase 3 clinical trial is planned to evaluate soquelitinib in patients with relapsed peripheral T cell lymphoma (PTCL).

• Soquelitinib was well-tolerated in a phase 1/1b trial (NCT03952078) with no dose-limiting toxicities observed.

The FDA has granted an orphan drug designation to soquelitinib for the treatment of patients with T-cell lymphoma, according to Corvus Pharmaceuticals, Inc.¹

Soquelitinib is a lead ITK inhibitor candidate. The oral, investigational small molecule drug is designed to selectively inhibit ITK, which is expressed in T cells. ITK also mediates T-cell and natural killer cell immune function.

A phase 3 registrational clinical trial is expected to launch in the second quarter of 2024 to evaluate soquelitinib in patients with relapsed PTCL.

“Peripheral T-cell lymphoma is an aggressive subset of non-Hodgkin lymphoma typically associated with a poor prognosis,” said Richard A. Miller, MD, co-founder, president, and chief executive officer of Corvus, in a news release. “For these patients, there is significant need for new therapies given that existing drugs provide limited efficacy and are associated with significant toxicity.

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At the 2022 American Society of Hematology Annual Meeting (ASH), interim data from a phase 1/1b trial were presented, showing soquelitinib to produce tumor responses among patients with advanced, refractory T-cell lymphomas.² Eleven patients with difficult-to-treat T-cell malignancies were included and among them, 1 patient achieved a complete response (CR), 1 patient had a nodal CR, and 2 patients had partial responses when treated with the agent twice daily at a dose of 200 mg. This dose was then identified as the optimal dose.

Further, safety findings showed soquelitinib to be well tolerated at doses up to 600 mg twice a day. There were no dose-limiting toxicities observed in the study.

Then at the 2023 ASH Annual Meeting, an analysis of the agent’s immune regulatory mechanism was presented from the ongoing, international phase 1/1b trial. Results showed soquelitinib to induce normal CD4-positive Th1 cells and CD8-positive TEMRA cells. The agent also reduced CD4-positive T regulatory cells in the tumor microenvironment in responding patients.⁴ Three of the 8 evaluable patients had disease progression and 4 patients achieved stable disease.

Adverse effects (AEs) that were observed in less than 1% of patients consisted of anemia, bilirubin increase, neutrophil count decrease, white blood cell decrease, and pruritus. AEs that were grade 3 or greater included 1 patient with neutrophil count decrease. With these findings, investigators believe that targeting specific molecular pathways in T cells with soquelitinib may hold potential across a variety of cancers, particularly solid tumors.¹

Now, the planned phase 3 trial of soquelitinib aims to enroll 150 patients with relapsed PTCL. Patients are required to have received no more than 3 prior therapies and they will be randomly assigned in a 1:1 fashion to receive either soquelitinib at the optimal 200 mg dose or standard-of-care chemotherapy.³

The primary end point of the study is progression-free survival, and key secondary end points are objective response rate and overall survival.

“There are no FDA-approved agents for relapsed PTCL,” added Miller in the press release.¹ “The orphan drug designation is an important milestone in the development of soquelitinib that reinforces the unmet need for patients with T-cell lymphoma.”

REFERENCES

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 12, 2024. http://tinyurl.com/2u72sedn

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 12, 2024. http://tinyurl.com/5bn79z6e

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