Linperlisib-Chidamide Combo Demonstrates Activity in Relapsed or Refractory CTCL

A novel combination to treat relapsed or refractory cutaneous T-cell lymphoma (CTCL) has shown promising results in a new study conducted by researchers at Peking Union Medical College Hospital in Beijing, China, led by Zhiyu Pang. Their research combining linperlisib, a PI3Kδ inhibitor, with chidamide, a histone deacetylase inhibitor, produced favorable outcomes with manageable safety for patients with relapsed or refractory CTCL.

In response to the limited treatment options for relapsed or refractory CTCL, it was hypothesized that using agents that act on different cancer-driven pathways together could improve treatment results without increasing toxicity.

This prospective, single-arm, phase 1, nonrandomized clinical trial focused on patients with histologically confirmed advanced CTCL and was conducted at a tertiary referral hospital in China from May 1, 2023, to March 6, 2025, with a median follow-up of 8.9 months (range, 1-21 months). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and received a median of three (range, 1-7) prior systemic therapies.

The study consisted of a 3+3 dose-escalation phase followed by dose expansion. Linperlisib was administered orally once daily in escalating doses (40 mg, 60 mg, or 80 mg) along with 20 mg of chidamide twice per week. The treatment continued until progression, unacceptable toxic effects, or withdrawal occurred.

The primary outcomes being explored in the study were dose-limiting toxic effects, maximum tolerated dose, and objective response rate; secondary outcomes included disease control rate, progression-free survival, and safety. Based on the results, an 80 mg dose of linperlisib was recommended for phase 2.

Of the 22 patients, 10 women and 12 men aged 27 to 71 years (median age, 44 years), 19 had mycosis fungoides, and three had Sézary syndrome. No dose-limiting toxic effects were observed, and treatment-related adverse events were mostly grade 1 or 2, with the most common being nausea in eight patients, pruritus in seven, and skin rash in seven. Grade 3 adverse events occurred in five patients, and no grade 4 or 5 events were reported.

The objective response rate was 59.1% (95% CI, 38.7%-76.7%), including two complete responses and 11 partial responses. The disease control rate was 86.4%, and median progression-free survival was 5.4 months.

Overall, the research suggests promising options in development of future treatment for relapsed or refractory CTCL. The researchers concluded that this all-oral combination therapy could represent an emerging treatment for advanced CTCL, with a focus on mycosis fungoides.