Study of Linperlisib Begins Dosing for R/R Peripheral T/NK Cell Lymphoma

A clinical trial investigating the efficacy and safety of linperlisib (YY-20394), a PI3K inhibitor, administered its first dose to a patient with (R/R PTCL), according to a press release from Yingli Pharma.¹

The single-arm, open-label, phase 2 study (NCT05274997) of linperlisib conducted in collaboration with The University of Texas MD Anderson Cancer Center aims to enroll 97 participants to evaluate linperlisib as monotherapy for this aggressive form of lymphoma.

“Linperlisib is a next generation inhibitor of delta isoform PI3K with enhanced selectivity and potency to offer strong anti-tumor effect while minimizing potential adverse reactions,” Michael Hui, MBA, CEO of Yingli Pharma, said in a statement. “We are encouraged by the safety and preliminary efficacy data obtained in phase 1 dose-finding studies in China and look forward to further evaluating linperlisib's potential in this phase 2 study.”

In the phase 2 trial, patients will receive an 80 mg daily dose of linperlisib orally in a 28-day cycle. The trial sites will include The University of Texas MD Anderson Cancer Center and other sites in the United States and Italy.

“We are pleased to be working with Yingli to initiate a phase 2 clinical trial evaluating linperlisib in patients with PTCL,” Swaminathan Iyer, MD, principal investigator and professor of lymphoma and myeloma at The University of Texas MD Anderson Cancer Center, said in a statement earlier this year.² “This collaboration brings a potentially effective treatment option with a favorable safety profile to the [United States] to address an unmet need for patients with this aggressive cancer. I look forward to leading this exciting study.”

Patients enrolled in this trial must have failed at least 1 prior systemic therapy, must not be eligible for stem cell transplant or brentuximab vedotin (Adcetris), and could not have central nervous system invasion. The primary end point is overall response rate (ORR) throughout the study for approximately 2 years. Secondary end points include duration of response, progression-free survival, overall survival, time to response, and adverse events (AEs).

Linperlisib is a highly selective and potent oral inhibitor that has previously shown efficacy in a phase 1b study of patients with R/R PTCL (NCT04108325) who received the recommended phase 2 dose of 80 mg once daily. In this trial, 19 out of 27 evaluable patients responded to linperlisib for an ORR of 70.4%, including 7 patients (25.9%) with a complete response.³ There was a 100% disease control rate, with most responses being seen at the first evaluation at the end of the second 28-day cycle.

The 80-mg dose was shown to be safe, with 95% of being grade 1 or 2 AEs and no grade 4 AEs observed. The most common treatment-related AEs were decreased neutrophil count (55.6%), decreased leukocyte count (33.3%), and hypertriglyceridemia (22.2%).

Linperlisib is also being investigated in different lymphoma subtypes and other diseases. Notably, it demonstrated an ORR of 80.9% (95% CI, 71.2%-88.5%) and a tolerable safety profile in patients with R/R follicular lymphoma in a phase 2 study (NCT04370405) in China.⁴ In the United States, it has received an orphan drug designation for T-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma.⁴

“Linperlisib may provide a solution for these patients who need an expanded treatment armamentarium, and we're excited to continue studying the drug's potential as we start the phase 2 study,” said Hui in the press release.¹

_REFERENCES

_{1. Yingli Pharma announces first patient dosed in phase 2 trial of linperlisib for peripheral T cell lymphoma. Yingli Pharma. September 3, 2022. Accessed September 8, 2022. https://prn.to/3BtqmUb}

_{2. MD Anderson and Yingli Pharma initiate strategic collaboration to advance development of multiple oncology programs. MD Anderson. January 20, 2022. Accessed September 9, 2022. https://bit.ly/3eCZ9p9}

_{3. Jin J, Cen H, Zhou K, et al. A phase Ib study of a PI3Kδ inhibitor linperlisib in patients with relapsed or refractory peripheral T-cell lymphoma. J Clin Oncol. 2021;39(15_suppl):7531. doi:10.1200/JCO.2021.39.15_suppl.7531}

_{4. Yingli Pharma announce promising topline results of a phase II registration study for treatment of relapsed/refractory follicular lymphoma with the once daily oral PI3Kδ inhibitor, linperlisib. Yingli Pharma. April 1, 2021. Accessed September 9, 2022. https://prn.to/3Den3kX}