Twice-daily treatment with Corvus Pharmaceuticals‘ potential therapy for T-cell lymphomas, CPI-818, is showing promising safety and tolerability, and preliminary signs of efficacy, according to Phase 1/1b results.
The early clinical data were shared at the 12th Annual T-Cell Lymphoma Forum, held recently in La Jolla, Calif. The presentation was titled “CPI-818, an Oral Interleukin-2-Inducible T-Cell Kinase Inhibitor. Pre-clinical Characterization and Interim Results of a Phase I/Ib Dose-Escalation Trial in Patients with Relapsed/Refractory T-Cell Lymphoma.”
CPI-818 is an oral therapy candidate for T-cell lymphomas — a type of cancer that develops in T-cells, which are a subset of immune system cells. It works by selectively stopping a protein called interleukin-2-inducible T-cell kinase (ITK), which plays an important role in mediating intracellular signaling.
The protein is a regulator of T-cell immunity against threats but is overactive in T-cell tumors, which leads to the uncontrolled and malignant growth of these cells. CPI-818 aims to both block the harmful T-cell overgrowth and to modulate immune responses.
The therapy is currently being tested in a Phase 1/1b clinical trial (NCT03952078), which is recruiting participants at 17 study locations in the United States, Australia, and South Korea. It seeks to enroll 151 participants with different types of T-cell lymphomas, including peripheral and cutaneous T-cell lymphomas, who have received at least two prior lines of therapy.
The study is assessing CPI-818’s safety, tolerability and anti-tumor activity, and will be conducted in two parts. In the dose escalation phase, patients will be included in groups of three and given ascending doses of CPI-818 — at 100, 200, 400, 600, 900, and 1200 mg — to determine the optimal dose for further testing.
The treatment will be given as an oral capsule, twice per day, until disease progression, complete response or remission (CR) for more than two months, or until the medication is deemed to be unsafe.
The dose expansion phase will then include four groups of patients who will receive the dose selected in the previous study phase. Those groups are peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), cutaneous T-cell lymphoma (CTCL), and other T-cell lymphomas. There will be 11 participants in each group, but on early signs of effectiveness, this number may be expanded to 28.
The early data was presented at the forum by Mehrdad Mobasher, MD, chief medical officer of Corvus. It included results from the first four dosage groups, given CPI-818 twice per day at 100 mg, 200 mg, 400 mg, or 600 mg. A total of 16 patients have been dosed and no dose-limiting toxicities or serious, treatment-related adverse events were observed, he said.
After a median follow-up of three months, 11 patients were still receiving treatment with CPI-818. Promising improvements were seen in two CTCL patients. One, treated with a 200 mg dose, saw a reduction in enlarged lymph nodes (lymphadenopathy), visible by PET scan imaging. Another patient receiving the 400 mg dose also experienced improvements in skin (cutaneous) disease. Both patients remain on therapy.
The results from the first 12 patients show that therapy behaves as expected, with target occupancy — or the number of ITK proteins being blocked — proportional to the dose used, based on results from the 100 mg, 200 mg, and 400 mg patient groups. The maximum target occupancy has not yet been reached. However, Corvus expects to achieve that aim with the recently initiated 600 mg dose group.
“Our Phase 1/1b clinical trial of CPI-818, our selective covalent ITK inhibitor designed to address T-cell lymphomas, is enrolling well and continues to provide promising clinical data for patients with advanced, refractory forms of this cancer,” Mobasher said in a press release.
“To-date, the data demonstrates that the biology and pharmacology of ITK inhibition with CPI-818 has been as expected and the trial is proceeding according to plan,” he said. “We are pleased to provide this update at the T-Cell Lymphoma Forum, a meeting dedicated to this difficult to treat family of cancers. We are now ready to advance the trial to higher drug doses where we will evaluate its activity in specific disease cohorts.”
The trial is expected to be completed in December 2022.
